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Biomedical subjects

F Lombardi

Publications and source records attributed to F Lombardi.

At least 37 records · Page 2Linked to original sources
PubMed2001

[The autonomic nervous system in myocardial infarction].

The occurrence of alterations in the autonomic control of cardiovascular function has long been known. Nevertheless, only in the last 15 years with the development and utilization of techniques such as heart rate variability and baroreflex analysis, unforeseeable amounts of information have been collected. The appraisal of alterations in the autonomic control mechanisms in the acute and post-acute phase of myocardial infarction has not only confirmed the presence of an increased sympathetic and of a reduced vagal modulation in most of post-myocardial infarction patients. It has also allowed the clinically relevant identification of those patients with an increased arrhythmic and total cardiac mortality. Most the high-risk patients are indeed characterized by a marked reduction in heart rate variability that can be detected using different methodologies. For example, with time-domain analysis of heart rate variability, it has been shown that an SDNN < 70 ms identifies patients at risk. By using spectral analysis, it has been possible to realize that the loss or marked attenuation of those rhythmical components that reflect autonomic modulation is also a characteristic of the high-risk patients. A decreased responsiveness of the sinus node to autonomic inputs may also explain the reduction in baroreflex sensitivity that characterizes patients with an increased arrhythmic mortality. In conclusion, the appraisal in each patient of the extent of the alterations in the autonomic control mechanism is nowadays a critical component of the clinical assessment not only for risk stratification but also in order to guide the prescription of new pharmacological and non-pharmacological therapies.

Autonomic Nervous System↗
PubMed2001

[Arrhythmia risk stratification in patients with heart failure: prognostic evaluation of arrhythmia risk].

Sudden cardiac death is one of the more frequent causes of death in patients with heart failure. Thus, identification of patients at risk is a major clinical problem not only for the unpredictability of the event but also for the continuous growth of patients' number. The most widely used parameter for risk stratification is ejection fraction. Unfortunately, its predictive accuracy is limited and often it is impossible to distinguish patients with an increased arrhythmic mortality from those with an increased mortality due to pump failure. Heart rate variability and baroreflex sensitivity analysis has been largely utilized to obtain information on autonomic modulation of sinus node as well as to identify patients at risk. However, at variance with results observed in post-myocardial infarction patients, lower values of both parameters have been reported in patients with either an increased total or arrhythmic mortality. More recently, T wave alternans analysis has been found effective in identifying patients with an increased arrhythmic risk. Ongoing studies will provide evidence to support the use of this non-invasive technique in patients with cardiac insufficiency. Finally, the role of programmed electrical stimulation in heart failure patients appears limited. Inducibility of monomorphic sustained ventricular tachycardia seems to correlate better with the presenting clinical arrhythmia than with patient outcome. In conclusion, our capability of identifying heart failure patients at risk for arrhythmic death is far from being satisfactory. It is possible that the combination of results of multiple non-invasive tests such as reduction in ejection fraction and positivity for T wave alternans may not only provide general prognostic information but also facilitate the appropriate identification of patients at risk who may benefit from antiarrhythmic therapy.

Arrhythmias, Cardiac↗
PubMed2000

Heart rate variability patterns before ventricular tachycardia onset in patients with an implantable cardioverter defibrillator. Participating Investigators of ICD-HRV Italian Study Group.

Time- and frequency-domain analysis of heart rate variability (HRV) has been proven effective in describing alteration of autonomic control mechanisms and in identifying patients with increased cardiac and arrhythmic mortality. Patients with implantable cardioverter defibrillators offer the opportunity to evaluate HRV patterns before ventricular tachycardia (VT) and under control conditions. We therefore analyzed time- and frequency-domain parameters of short-term HRV and power-law behavior of RR interval time series at rest, at 15 to 30 minutes, and immediately before VT. In comparison to control conditions, lower values of mean cycle length duration and total power were observed before VT. Spectral analysis indicated that the low- to high-frequency ratio was significantly higher (5.5 +/- 0.6 vs 2.8 +/- 0.3) immediately before VT than during rest. Both findings were consistent with the shift of sympathovagal balance toward sympathetic predominance and reduced vagal tone. Before VT, a more negative value of the scaling exponent beta of the power-frequency relation (-1.57 +/- 0.04 vs -1.33 +/- 0.04) also confirmed the presence of an altered HRV pattern in comparison to controls. Thus, both abnormal autonomic modulation and dynamic patterns of HRV seem to characterize the minutes before arrhythmia onset in these patients.

Aged↗
PubMed2000

Successful in vivo purging of CD34-containing peripheral blood harvests in mantle cell and indolent lymphoma: evidence for a role of both chemotherapy and rituximab infusion.

Elimination of tumor cells ("purging") from hematopoietic stem cell products is a major goal of bone marrow-supported high-dose cancer chemotherapy. We developed an in vivo purging method capable of providing tumor-free stem cell products from most patients with mantle cell or follicular lymphoma and bone marrow involvement. In a prospective study, 15 patients with CD20(+) mantle cell or follicular lymphoma, bone marrow involvement, and polymerase chain reaction (PCR)-detectable molecular rearrangement received 2 cycles of intensive chemotherapy, each of which was followed by infusion of a growth factor and 2 doses of the anti-CD20 monoclonal antibody rituximab. The role of rituximab was established by comparison with 10 control patients prospectively treated with an identical chemotherapy regimen but no rituximab. The CD34(+) cells harvested from the patients who received both chemotherapy and rituximab were PCR-negative in 93% of cases (versus 40% of controls; P =.007). Aside from providing PCR-negative harvests, the chemoimmunotherapy treatment produced complete clinical and molecular remission in all 14 evaluable patients, including all 6 with mantle cell lymphoma (versus 70% of controls). In vivo purging of hematopoietic progenitor cells can be successfully accomplished in most patients with CD20(+) lymphoma, including mantle cell lymphoma. The results depended on the activity of both chemotherapy and rituximab infusion and provide the proof of principle that in vivo purging is feasible and possibly superior to currently available ex vivo techniques. The high short-term complete-response rate observed suggests the presence of a more-than-additive antilymphoma effect of the chemoimmunotherapy combination used.

Adult↗
PubMed2000

Management of medulloblastoma and ependymoma in infants: a single-institution long-term retrospective report.

To reduce the sequelae from CNS irradiation (RT), 16 children younger than 3 years with medulloblastoma-PNET (13 cases) and ependymoma (3 cases) were treated between 1987-1993 according to different postsurgical chemotherapy (CT) programs. None of these patients presented with metastases. Eleven patients were rendered disease-free by surgery, while 5 had residual tumor. Adjuvant therapy depended on patients' age, postsurgical status and parents' consent to radiotherapy (RT). Nine of the 16 infants remained alive in continuous complete remission from the first neoplasm (median follow-up 7 years). Three of them had been treated with CT alone and 6 with combined CT + RT (posterior fossa 4, whole CNS 2). Seven patients relapsed a median of 13 months after diagnosis, and all 7 of them died of their disease. Despite the omission of RT in 6 of the 16 patients and administration of only focal RT in 8 of the 16, the outcome of this series was satisfactory. Local failure (in 5/7 patients) was the major problem, despite the high dose of RT used in 2 of these 5. In 4 of 6 evaluable children school performance was satisfactory. One child in whom the entire CNS was irradiated developed glioblastoma multiforme 120 months after the first diagnosis of medulloblastoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Role of the input/output relation of sinoatrial myocytes in cholinergic modulation of heart rate variability.

INTRODUCTION: Modulation of sinus rate may be viewed as the transduction of an input signal (receptor stimulation) into an output signal (cycle length [CL]) by the sinus node. This study analyzes the input/output (I/O) relation of sinoatrial pacemaking elements and tests its impact on cholinergic modulation of heart rate variability. METHODS AND RESULTS: Spontaneous activity of isolated rabbit sinoatrial myocytes was recorded by patch clamp techniques. CL and all the action potential parameters determining CL were automatically measured from >100 consecutive cycles. Acetylcholine (ACh, 5 to 50 nM) increased CL by decreasing diastolic depolarization rate (DDR) only. This was associated with a substantial increase in the coefficient of variation of CL and minor changes in the coefficient of variation of other parameters. A simple function relating CL to action potential parameters accurately described CL response to ACh (I/O relation). Numerical simulations based on this I/O relation showed that ACh-induced depression of DDR might, by its own, increase CL variability. CONCLUSION: Time-domain measurements of CL variability may not necessarily reflect variability of the neural input to the sinoatrial node, but also may be affected by its tonic level. Properties of the I/O relation of sinoatrial myocytes may fully account for the dependency of CL variability on mean heart rate, previously described in humans. Any condition depressing DDR may enhance CL variability, independent of changes in the pattern of neural activity.

Acetylcholine↗
PubMed2000

Non-pulmonary effects induced by the addition of formoterol to budesonide therapy in patients with mild or moderate persistent asthma.

OBJECTIVE: The present study was designed to assess the non-pulmonary effects of a 2-week treatment with the addition of formoterol to budesonide therapy in 10 patients with mild or moderate asthma. METHODS: Each patient was invited to perform a screening visit which included spirometry before and after inhalation of 12 microg formoterol with a metered dose inhaler (MDI), measurement of arterial blood pressure, baseline electrocardiography and 24-hour Holter monitoring, and a test for evaluating upper limb tremor. Patients then began bronchodilating therapy with 12 microg formoterol MDI and 400 microg budesonide Turbuhaler b.i.d. Each patient was also given a peak flowmeter and a diary in which he had to record the morning and evening values measured before taking inhaled drugs. Two weeks later, the patients repeated the same examinations; the diary card was returned 2 months after the beginning of the study. RESULTS: Adding formoterol to budesonide therapy caused a significant improvement in lung function, but neither induced any statistically significant effect on mean heart rate, nor altered the circadian rhythm of autonomic regulation nor elicited significant alterations in cardiac morphology. However, the evaluation of upper limb tremor revealed a statistically significant increase (p = 0.02). CONCLUSIONS: This study shows that adding the recommended dose of formoterol to an inhaled corticosteroid therapy does not induce significant cardiac undesirable effects, although tremor, surely due to stimulation of beta(2) receptors of the skeletal muscles, may sometimes be a limiting effect.

Adrenergic beta-Agonists↗
PubMed2000

[Detection and assessment of myocardial stunning with perfusion tomographic scintigraphy using gated SPECT].

BACKGROUND: Gated-SPECT using 99mTc-labeled flow tracers provides the simultaneous assessment of global and regional myocardial perfusion and function. The aim of this study was to identify patients with stress-induced postischemic stunning, among those with reversible stress perfusion defects, and patients with artifactual defects among those with fixed defects, in order to assess the value of the functional data provided by gated acquisition of perfusion imaging in the characterization of ischemia. METHODS: We studied 221 consecutive patients who underwent conventional diagnostic dual day stress/rest gated-SPECT following injection of 925 MBq of 99mTc-tetrofosmin using a dual head SPECT camera, 115 of whom (52%) showed reversible perfusion defects, and 66 (30%) fixed defects. Perfusion was analyzed on ungated images using 20 segments scored on a 5-point scale (0 = normal, 4 = no uptake), while wall thickening was assessed visually on stress/rest end-systolic images using a 4-point score (0 = normal, 3 = absence of wall thickening). Left ventricular ejection fraction and volumes were calculated using an automatic algorithm (quantitative gated-SPECT). Fifty-two out of 221 (23.5%) patients underwent coronary angiography. RESULTS: In 40/115 (35%) patients with reversible perfusion defects, post-stress left ventricular ejection fraction was > 5% lower than that at rest (Group A: stunned), whereas in the remaining 75 patients, post-stress left ventricular ejection fraction was either +/- 5% or greater than that at rest (Group B: non-stunned). Peak exercise angina and ischemic electrocardiographic response to exercise were present in 79 and 58% respectively of Group A patients and in 33 and 39% of Group B patients. The number of patients with multivessel disease was significantly higher in Group A compared to Group B (58 vs 41%, p < 0.05). The total stress and rest perfusion scores were significantly higher in Group A than in Group B (p < 0.01); even the total stress wall thickening score was significantly higher in Group A (p < 0.001). As for global parameters, post-stress end-systolic volume was significantly higher in the stunned group (p < 0.05). In 40 out of 66 (60.5%) patients without reversible ischemia fixed defects were judged to be ischemic (Group C), while in 26/66 (39.5%) they were attributed to attenuation artifacts (Group D). Eighty percent of Group C patients had a previous myocardial infarction against none of Group D. Stress/rest perfusion and wall thickening scores were significantly higher in Group C than in Group D. CONCLUSIONS: Gated-SPECT myocardial perfusion evaluation allowed us to identify a subgroup of post-stress stunned coronary artery diseased patients. The post-stress left ventricular ejection fraction reduction in this population seems to be due to the increase in end-systolic volume. The stunned patients showed more severe perfusion defects and wall thickening abnormalities.

Exercise Test↗
PubMed1999

Synovial sarcoma: report of a series of 25 consecutive children from a single institution.

BACKGROUND: The role of postoperative radiotherapy and adjuvant chemotherapy in the treatment of synovial sarcoma remains to be determined. PROCEDURE: Twenty-five children were treated during a 23-year period with a multimodality approach. All of them had resection of the primary tumor (three amputations), followed by surgical retreatment in eight. Postoperative radiotherapy was delivered to 16 patients and adjuvant chemotherapy was given to 22. RESULTS: At the time of the report, 19 patients were alive and without evidence of disease. Six developed distant metastases (one associated with local recurrence); five of them died of their disease and one was alive in complete remission at 4 years from relapse. With a median follow-up of 9 years (range 2-23), the survival and the event-free survival at 5 years were 80% (SE 8.2) and 74% (SE 9.2), respectively. All relapsing patients had been classified as T2B. CONCLUSIONS: Multimodality treatment yielded satisfying survival results using limb-preserving surgery in most cases. Tumor size > 5 cm and invasiveness, which defined stage T2B, were the most important predictors of poor outcome. Evaluation of the role of adjuvant chemotherapy and radiotherapy awaits prospective studies, even if T2B patients, as well as children having nonradical surgery, seem worth managing by adjuvant treatments.

Adolescent↗
PubMed1999

Conditional entropy approach for the evaluation of the coupling strength.

A method that enables measurement of the degree of coupling between two signals is presented. The method is based on the definition of an uncoupling function calculating, by means of entropy rates, the minimum amount of independent information (i.e. the information carried by one signal which cannot be derived from the other). An estimator of the uncoupling function able to deal with short segments of data (a few hundred samples) is proposed, thus enabling the method to be used for usual experimental recordings. A synchronisation index is derived from the estimate of the uncoupling function by means of a minimisation procedure. It quantifies the maximum amount of information exchanged between the two signals. Simulations in which non-linear coordination schemes are produced and changes in the coupling strength are artificially induced are used to check the ability of the proposed index to measure the degree of synchronisation between signals. The synchronisation analysis is utilised to measure the coupling strength between the beat-to-beat variability of the sympathetic discharge and ventilation in decerebrate artificially ventilated cats and the degree of synchronisation between the beat-to-beat variability of the heart period and ventricular repolarisation interval in normal subjects and myocardial infarction patients. The sympathetic discharge and ventilation are strongly coupled and the coupling strength is not affected by manoeuvres capable of increasing or depressing sympathetic activity. The synchronisation is lost after spinalisation. The synchronisation analysis confirms that the heart period and ventricular repolarisation interval are well coordinated. In normal subjects, the synchronisation index is not modified by experimental conditions inducing changes in the sympathovagal balance. On the contrary, it strongly decreases after myocardial infarction, thus detecting and measuring the uncoupling between the heart period and ventricular repolarisation interval.

Animals↗
PubMed1999

Subcutaneous administration of interleukin-2 and interferon-alpha 2b in advanced renal cell carcinoma: long-term results.

Clinical data have supported the combination of subcutaneous r-interleukin-2 (rIL-2) and r-interferon-alpha (rIFN-alpha) as a promising combination for advanced renal cell carcinoma (RCC), with a reduced toxicity. We evaluated the activity and safety of this outpatient immunotherapy and report on the clinical results and the long-term survival analysis. Objective responses was observed in 9 of 50 (18%) patients, 6 of whom (12%) achieved a complete response. Overall median survival is 12 months, six patients were surviving at a median follow-up of 24 months, and three (6%) are still progression-free.

Adult↗
PubMed1999

Myocardial viability assessment after acute myocardial infarction: low-dose dobutamine echocardiography versus rest-redistribution thallium-201 SPECT.

BACKGROUND: The presence of tissue viability is of great importance in the prognostic work-up of patients recovering from acute myocardial infarction. However, uncertainty still exists concerning the optimal tool for its assessment. The present study was undertaken in order to compare low-dose dobutamine echocardiography and rest-redistribution thallium SPECT for predicting late improvement of regional left ventricular function after acute myocardial infarction. METHODS: Fifteen patients undergoing coronary angiography, low-dose dobutamine echocardiography and rest-redistribution thallium SPECT after thrombolyzed anterior acute myocardial infarction were studied. A 3 month follow-up echocardiogram was performed in all patients and 9 underwent coronary revascularization. RESULTS: A significant (> or = 70%) residual stenosis of the infarct-related artery was present in 14 patients, whilst a total occlusion was observed in 1. At 3 month follow-up, 41% of the dyssynergic segments improved. The sensitivity, specificity and accuracy for late wall motion improvement was 61, 89 and 77% for low-dose dobutamine echocardiography and, respectively, 76, 45 and 58% for rest-redistribution thallium SPECT. Tissue viability was detected in 65 and 31% of dyssynergic segments by rest-redistribution thallium SPECT and low-dose dobutamine echocardiography, respectively (p < 0.001). The agreement between the two techniques was 48%. CONCLUSIONS: Low-dose dobutamine echocardiography is more accurate than rest-redistribution thallium SPECT for predicting 3 month wall motion improvement in patients with acute anterior myocardial infarction, mainly due to its significantly better specificity.

Adult↗
PubMed1998

Comparison between noninvasive indices of baroreceptor sensitivity and the phenylephrine method in post-myocardial infarction patients.

BACKGROUND: Depressed baroreflex sensitivity obtained by means of a phenylephrine test plays a prognostic role in patients with a previous myocardial infarction. Our purpose was to evaluate the correlation and agreement between the baroreflex sensitivity obtained with phenylephrine and that obtained by two noninvasive methods: the alpha-index and sequence analysis. METHODS AND RESULTS: The alpha-index was measured by means of the spectral analysis of RR and systolic blood pressure variabilities in both the high- and low-frequency bands; sequences were identified from simultaneously recorded time series in which the RR and systolic blood pressure concurrently increased or decreased. Noninvasive baroreflex sensitivity tests were performed during both spontaneous and controlled respiration. Fifty-two consecutive patients with recent myocardial infarction underwent the analyses. Although the correlations between phenylephrine and either of the noninvasive methods were always significant, those found during controlled respiration had the highest r values (r=.70). However, the limits of agreement calculated by means of the Bland and Altman method were wide for both noninvasive methods. CONCLUSIONS: The results obtained by means of noninvasive baroreflex sensitivity assessments should not be used in clinical practice as an alternative to those obtained by the phenylephrine method.

Adult↗