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Biomedical subjects

G Di Pasquale

Publications and source records attributed to G Di Pasquale.

At least 19 recordsLinked to original sources
PubMed1999

Pro-apoptotic effect of fluvastatin on human smooth muscle cells.

The antiatherosclerotic effect of statins has been attributed to their hypocholesterolemic action. We therefore evaluated the effect, in vitro, of the addition of the serum of patients taking fluvastatin on human smooth muscle cells in order to ascertain the effect of the drug on cell proliferation and apoptosis. We found that the addition of serum from patients treated with fluvastatin for 6 days caused a significant reduction in cell proliferation, increased cell apoptosis and reduced the B cell leukemia-2 (bcl-2) concentration. It is concluded that the induction of apoptosis by statins could be a supplementary mechanism in the prevention of atherosclerotic lesions in humans.

Adult↗
PubMed1999

Reduced bcl-2 concentrations in hypertensive patients after lisinopril or nifedipine administration.

In 30 patients with essential hypertension and 30 healthy control subjects, we evaluated blood concentrations of B cell leukemia-2 (bcl-2), a protooncogene that can reduce apoptosis. Bcl-2 concentrations were higher in hypertensive than in normotensive subjects. The increase in pressure due to a cold pressor test caused a further increase in blood bcl-2 concentrations, in both hypertensive and normotensive subjects. Treatment of hypertensive patients with hypotensive drugs caused a reduction in bcl-2 concentrations, which was more marked after administration of lisinopril than of nifedipine. The results suggest that concentrations of bcl-2 are increased in patients with hypertension, which could be an important factor in cell proliferation underlying posthypertensive vascular remodeling. Moreover, lisinopril and nifedipine appear to be capable of reducing bcl-2 concentrations, with potentially beneficial effects on vascular modifications in patients with hypertension.

Administration, Oral↗
PubMed1998

Adeno-associated virus Rep78 protein interacts with protein kinase A and its homolog PRKX and inhibits CREB-dependent transcriptional activation.

Adeno-associated virus (AAV) is a human parvovirus of the genus Dependovirus. AAV replication is largely restricted to cells which are coinfected with a helper virus. In the absence of a helper virus, the AAV genome can integrate into a specific chromosomal site where it remains latent until reactivated by superinfection of the host cell with an appropriate helper virus. Replication functions of AAV have been mapped to the Rep68 and Rep78 gene products. Rep proteins demonstrate DNA binding, endonuclease, and helicase activities and are involved in regulation of transcription from both AAV and heterologous promoters. AAV has been associated with suppression of oncogenicity in a range of viral and nonviral tumors. In this study we sought to identify and study cellular protein targets of AAV Rep, in order to develop a better understanding of the various activities of Rep. We used the yeast two-hybrid system to identify HeLa cell proteins that interact with AAV type 2 Rep78. We isolated several strongly interacting clones which were subsequently identified as PRKX (previously named PKX1), a recently described homolog of the protein kinase A (PKA) catalytic subunit (PKAc). The interaction was confirmed in vitro by using pMal-Rep pull-down assays. The region of Rep78 which interacts was mapped to a C-terminal zinc finger-like domain; Rep68, which lacks this domain, did not interact with PRKX. PRKX demonstrated autophosphorylation and kinase activity towards histone H1 and a PKA oligopeptide target. Autophosphorylation was inhibited by interaction with Rep78. In transfection assays, a PRKX expression vector was shown to be capable of activating CREB-dependent transcription. This activation was suppressed by Rep78 but not by Rep68. Since PRKX is a close homolog of PKAc, we investigated whether Rep78 could interact directly with PKAc. pMal-Rep78 was found to associate with purified PKAc and inhibited its kinase activity. Cotransfection experiments demonstrated that Rep78 could block the activation of CREB by a PKAc expression vector. These experiments suggest that AAV may perturb normal cyclic AMP response pathways in infected cells.

Catalysis↗
PubMed1998

Reduced blood bcl-2 protein concentration in patients on hemodialysis.

The concentrations of bcl-2 protein that can block programmed cellular death in various cell lines were evaluated in blood samples from 10 uremic patients on hemodialysis, 10 uremics not yet on hemodialysis, and in 10 healthy controls. The bcl-2 protein variations (in uremics on dialysis) were ascertained in patients during the dialysis session. Oxidative stress was evaluated in all groups by assaying the products of intraerythrocytic lipoperoxidation. Dialyzed and nondialyzed uremic patients had higher bcl-2 protein concentrations than healthy subjects. Dialysis causes a significant reduction in the concentrations of bcl-2 protein which becomes statistically significant during the 3rd hour. In both groups of uremic patients a positive correlation was found between bcl-2 protein and products of lipoperoxidation.

Aged↗
PubMed1998

Cardiologic complications of subarachnoid hemorrhage.

Cardiac complications are frequent in patients with subarachnoid hemorrhage (SAH). They include ECG abnormalities, cardiac arrhythmias, myocardial damage, and neurogenic pulmonary edema. The pathophysiology of these abnormalities is related to an imbalance of the autonomic cardiovascular control and to increased circulating and local myocardial tissue catecholamines. Cardiac involvement is more common in patients with severe neurological deficits and it may increase the morbidity associated with SAH because of the occurrence of life-threatening arrhythmias or pulmonary edema. Monitoring of cardiac events in patients with SAH might result in a better understanding of their clinical outcome, as well as providing a basis for specific treatment capable of preventing myocardial necrosis and cardiac arrhythmias.

Arrhythmias, Cardiac↗
PubMed1998

[AI-CARE: a multicentric study on unstable angina. Methodology and preliminary data of a project on the improvement of health care quality in Emilia-Romagna].

BACKGROUND: Recent Italian legislative directives have focused on lowering health-service costs and improving the quality of health care. The AI-CARE study on unstable angina represents the initial observational step in a survey on health-care quality in the Italian region Emilia-Romagna. AIM OF THE STUDY: This study was performed to identify the processes usually involved in the management of patients with unstable angina admitted to a regional cardiology department. The consumption of health service resources and the clinical events related to angina were evaluated. METHODS: AI-CARE is an observational, descriptive and prospective study. Between 15/3/95 and 15/6/95, the patients admitted consecutively to 25 cardiology units for unstable angina, as diagnosed on a clinical basis, were enrolled in the study. A six-week follow-up was provided. The data regarding demographics, history, entry electrocardiogram, symptoms, examinations, treatment and outcome were recorded on a detailed personal questionnaire. The participating centers have been divided according to complexity of organization: 18 with intensive care unit as level I, five with hemodynamic laboratory as level II and two with cardiosurgery as level III. Mortality, myocardial infarction, revascularization procedures and readmissions for angina were considered clinical events. RESULTS: We recruited 463 patients. At discharge, 411 patients were affected with unstable angina while other 40 developed non-Q wave infarctions. The final study population comprised 451 patients. The mean age was 68 years (range 61-76). There were 316 men (69%, mean age 68) and 135 women (mean age 72). All 451 patients were stratified according to the Braunwald classification: IIIB in 66.9%, IIIC in 9.9%, IB in 9.9%. Mean hospital stay was 10 +/- 6 days, while mean stay in intensive care units was 4.3 +/- 2.9 days. Medical treatment included antiplatelet agents (89%), nitrates i.v. (81%), nitrates per os (86%), heparin (55%) and beta-blockers (47%). The most common non-invasive test performed was echocardiogram (70% of patients), Holter ECG and exercise stress testing (19%). Selective coronary arteriography was performed in 50% of patients (23% during the first 10 days). Additionally, 32% of patients underwent revascularization. During follow-up, ten patients (2.21%) had a myocardial infarction, nine patients (1.99%) died and 49 patients (10.8%) were readmitted for angina. CONCLUSIONS: This study indicates that in spite of the poor use of diagnostic procedures (especially coronary arteriography) and myocardial revascularization, mortality and morbidity were relatively low. Our data are similar to the results of the recent Italian EARISA study but differ greatly from the results of foreign studies. Consequently, further observation of our study population is needed.

Aged↗
PubMed1998

[Platelet antiaggregants or anticoagulants in the secondary prevention after myocardial infarct].

Aspirin and oral anticoagulants are effective treatments in the secondary prevention after myocardial infarction. Aspirin at the dosage of 160-325 mg per day accomplishes a 21% reduction of the recurrences of vascular events (INR: 3-4). Oral anticoagulants are likely to be more effective; this therapy however is more demanding for the patient and the referring physician and is associated with a higher risk of hemorrhage. According to the available information from the literature, aspirin should be recommended for the majority of patients surviving after myocardial infarction. Oral anticoagulants should be reserved for post-infarction patients at high risk of thromboembolism and for those patients who present either intolerance to aspirin or recurrence of vascular events during aspirin treatment.

Administration, Oral↗
PubMed1997

Type and extent of myocardial injury related to brain damage and its significance in heart transplantation: a morphometric study.

BACKGROUND: Focal myocardial necrosis reported in patients who died of brain lesions and in donor hearts soon after insertion has been attributed to catecholamine-related injury induced before operation, or in the perioperative period. Interpretation of the morphofunctional type of myocardial injury observed and its quantification may help understand both its pathophysiology and clinical relevance. METHODS: In 27 patients without heart disease who died of intracranial brain hemorrhage after berry aneurysm rupture, terminal clinical signs were correlated with the presence of absence of myocardial injury. All hearts were systematically examined, and the total histologic area was measured in square millimeters, with both the number of foci and myocardial cells showing necrosis, normalized to 100 mm2. Forty-five cases of fatal head trauma (26 "instantaneous" and 19 "rapid" deaths) in normal subjects and 38 cases of acquired immunodeficiency syndrome with (14 cases) or without (24 cases) severe brain damage were used as control subjects. RESULTS: Contraction band necrosis was the only form of myocardial necrosis found in 89% of patients with acute brain hemorrhage. Its extent was 26 +/- 34 foci and 67 +/- 104 necrotic myocardial cells x 100 mm2. In patients with acquired immunodeficiency syndrome, its frequency was 58% in those without and 78.5% with severe brain lesions, with foci and myocardial cell values of 1 +/- 1.5 and 10 +/- 22 and 7 +/- 16 and 17 +/- 32, respectively. In head trauma cases with instantaneous death, the frequency was 4% (one case only with foci 0.5 and myocardial cells 35), whereas with a rapid death it was 40% (foci 12 +/- 18 and myocardial cells 21 +/- 33). CONCLUSIONS: The observed myocardial injury was present in all groups examined, being maximal in patients with intracranial brain hemorrhage with longer survival and minimal in patients with head trauma who died instantaneously. In this setting, this lesion is typical of catecholamine myotoxicity and may express a sympathetic overstimulation either in the agonal period and independent of therapy or be caused by brain injury, especially intracranial brain hemorrhage. However, the extent of myocardial injury observed was minimal and should not jeopardize cardiac function if hearts from such subjects are transplanted.

AIDS Dementia Complex↗
PubMed1996

Transient sympathovagal imbalance triggers "ischemic" sudden death in patients undergoing electrocardiographic Holter monitoring.

OBJECTIVES: The aim of this study was to investigate the relation between "ischemic" sudden death (arrhythmic death preceded by ST segment shift) and autonomic nervous system activity. Background. Mechanisms precipitating sudden death are poorly known despite the importance of detecting functional factors that may contribute to such a fatal event. METHODS: We analyzed the tapes of eight patients (seven men and one woman with a mean age of 66 +/- 8 years) who had ischemic sudden death during ambulatory electrocardiographic (Holter) monitoring. Four patients had unstable and four had stable angina; none was taking antiarrhythmic drugs. Twenty patients with angina and transient myocardial ischemia during Holter monitoring served as control subjects. Arrhythmias, ST segment changes and heart rate variability were analyzed by a computerized interactive Holter system. RESULTS: Five patients had ventricular tachyarrhythmias (ventricular fibrillation in three, ventricular tachycardia in two), and three had bradyarrhythmias (atrioventricular block in two, sinus arrest in one) as the terminal event; all eight patients showed ST segment shift (maximal change 0.46 +/- 0.16 mV; with ST elevation in two) that occurred 41 +/- 34 min (mean +/- SD) before sudden death. The standard deviation of normal RR intervals (SDNN) was 89 +/- 33 ms during the 10 +/- 6 h of Holter monitoring; 5 min before the onset of the fatal ST shift, SDNN measurements were significantly lower than during the initial 5-min period (48 +/- 10 vs. 29 +/- 9 ms; p=0.002). In control patients, the SDNN was 102 +/- 39 ms during Holter monitoring, whereas it measured 56 +/- 30 ms 5 min before the most significant episode of ST shift (p<0.01 vs. 29 +/- 9 ms [corrected] in the group with sudden death). CONCLUSIONS: Autonomic dysfunction, as detected by a marked decrease in heart rate variability, is present in the period (5 min) immediately preceding the onset of the ST shift precipitating ischemic sudden death. These data suggest that sympathovagal imbalance may trigger fatal arrhythmias during acute myocardial ischemia, thus resulting in sudden death.

Aged↗
PubMed1996

[Prognostic significance of normal exertion myocardial scintigraphy in asymptomatic subjects with abnormal ergometric test].

AIM OF THE STUDY: ST-segment depression on exercise stress test (EST) is an independent predictor of future cardiac events. Nevertheless, in apparently healthy subjects without angina the occurrence of false positive results is frequent. Thallium myocardial imaging (TMI) may improve diagnostic and prognostic accuracy of EST. The aim of the present study was to assess the role of a normal exercise TMI for excluding a coronary artery disease in subjects with asymptomatic abnormal EST. METHODS: Subjects referred for TMI from 1/1980 to 5/1991 with an abnormal EST and without history of ischemic, congenital, or valvular heart disease or abnormal resting ECG were included into the study. 137 subjects (98 men, 39 women), mean age 53 +/- 8 yrs (range 37-74 yrs) were enrolled and followed-up for 6.4 yrs (range 3-13 yrs). Clinical indications for EST were: atypical chest pain in 56 (41%) cases, check-up in 52 (38%) cases, sport activity in 29 (19%) cases. All subjects had a maximal symptom-limited EST. Abnormal EST was defined by a horizontal or downsloping > or = 1 mm or upsloping > or = 1.5 mm ST-segment depression at 0.08 sec. from J-point, in at least 2 leads. EST was discontinued for fatigue in 129 (94%) cases, for ST-segment depression > or = 3 mm in 8 (6%) cases. None had chest pain during EST. All subjects selected for the study had normal TMI. Criteria for normal TMI were homogeneous Thallium uptake on postexercise images and a normal washout in the delayed images by qualitative analysis. Planar images were obtained in 118 (86%) cases, and tomographic SPECT images in 19 (14%). RESULTS: During the follow-up period no subject died for cardiac causes and only 9 subjects (1%/yr) had non fatal cardiac events: 4 (0.45%/yr) had a non fatal myocardial infarction (one subject had coronary angiography for postinfarction angina and subsequent 3 coronary bypass graft for multivessels disease), 2 subjects (0.2%/yr) became symptomatic for unstable angina (both had coronary angiography and subsequent PTCA for critical left main coronary artery stenosis) and 3 (0.34%/yr) developed stable angina (one had coronary angiography and subsequent bypass graft for a critical stenosis of left main coronary artery). Four further subjects died for non cardiac events. Comparing clinical data and TE results of subjects with and without coronary events, we found that some parameters were related to a higher incidence of cardiac events: hypertension (78% vs 31% respectively in subjects with and without cardiac events, p < 0.01), hypercholesterolemia (33% vs 4.7%, p < 0.01); > or = 2 conventional coronary risk factors (56% vs 17%, p < 0.02); and a slow regression of abnormal ST-segment depression during recovery (2.8 +/- 2 vs 1.5 +/- 1 min, p < 0.01). CONCLUSIONS: In conclusion, in subjects without typical chest pain and with abnormal asymptomatic EST, a normal exercise TMI identifies subjects with very low risk of future cardiac events (1%/yr). Our data suggest that subjects with abnormal asymptomatic EST should be routinely submitted to exercise TMI.

Adult↗
PubMed1995

[A transient decrease in heart rate variability in patients with sudden "ischemic" death during Holter monitoring].

BACKGROUND: Mechanisms precipitating sudden death are poorly known, in spite of the importance to detect functional factors which may contribute to such fatal event. Aim of the study was to investigate the relationship between "ischemic" sudden death (ISD: arrhythmic death preceded by acute myocardial ischemia) and autonomic nervous system activity. METHODS: We analysed the tapes of 6 patients (pts) (5 males; 67 +/- 12 yrs) suffering ISD during Holter monitoring (HM). One pt had recent onset angina, 2 had unstable and 3 stable angina; none was taking antiarrhythmic drugs. Arrhythmias, ST segment and heart rate variability (HRV) were analysed by a computerized interactive HM system, in order to obtain data on transient ischemia and sympatho-vagal balance. RESULTS: Five pts showed ventricular tachyarrhythmias (2 VF, 3 VT), and 1 had a bradyarrhythmia (advanced A-V block) as the terminal event; all pts showed ST shift (max: 0.37 +/- 0.28 mV; 1 with ST elevation; 4 with anginal pain) 53 +/- 35 min before ISD. SD of normal R-R intervals (SDNN) was 112 +/- 26 msec in the 11 +/- 8 hrs of HM, whereas it was 97 +/- 48 msec in the initial hour and 59 +/- 21 msec in the initial 5 min segment. Measurements of SDNN showed a marked decrease 5 min before the onset of fatal ischemic ST shift: 32 +/- 14 msec (p = 0.003). Also, pNN50 (percent of adjacent R-R differing > 50 msec: marker of vagal activity) was significantly reduced before ISD, when compared to the initial 5 min segment (from 10 +/- 5 to 7 +/- 4%; p < 0.03). Such changes were not observed before uncomplicated (that is not associated with malignant arrhythmias) ST shift episodes during HM. CONCLUSIONS: Autonomic dysfunction, as detected by a marked decrease of HRV, is present in the period (5 min) immediately preceding the onset of ST shift precipitating ISD; simultaneous measurements of vagal signals showed similar changes. These data suggest that sympatho-vagal unbalance may trigger fatal arrhythmias during acute myocardial ischemia, hence resulting in ISD.

Aged↗
PubMed1995

[Multiple spontaneous coronary dissection. Case report and review of the literature].

We refer a case of a 57-year-old woman with an acute myocardial infarction of the anterior wall, treated with rt-PA, aspirin and heparin. In the following days, in spite of the therapy, occurred a second acute myocardial infarction of the inferior wall complicated with ventricular fibrillation. Coronary angiography showed multiple coronary dissection involving the left anterior descending and the circumflex coronary arteries. The characteristic feature of this case consists of the multiple coronary dissection responsible for myocardial infarctions, an event seldom reported in the literature.

Aortic Dissection↗
PubMed1994

Preoperative noninvasive coronary risk stratification in candidates for carotid endarterectomy.

BACKGROUND AND PURPOSE: Patients with symptomatic carotid stenosis who are candidates for carotid endarterectomy are at high short- and long-term risk of coronary events. To stratify patients at different risk of coronary events we investigated the usefulness of a noninvasive preoperative cardiological workup. METHODS: We studied 172 consecutive patients admitted to the Neurosurgical Department for symptomatic high-grade (70% to 99%) carotid stenosis (age, 42 to 74 years; mean, 57.8 years). Patients without history of coronary artery disease (CAD) and able to exercise were submitted to exercise electrocardiographic testing (EET) and, if abnormal, to exercise thallium myocardial imaging (TMI). Patients were classified into four groups: group 1, patients without CAD: no history of CAD, normal EET, or normal TMI in the presence of indeterminant EET (n = 93, 54%); group 2, patients with silent CAD: no history of CAD and concordant abnormal EET and TMI (n = 28, 16%); group 3, patients unable to exercise: no history of CAD and inability to perform adequate EET because of previous stroke or claudication (n = 29, 17%); and group 4, patients with known CAD: history of angina or myocardial infarction (MI) (n = 22; 13%). RESULTS: The four groups were comparable in regard to age, sex, and computed tomographic scan of the brain. The prevalence of stroke was higher in patients unable to exercise; hypercholesterolemia was more frequent in patients with known CAD. During the perioperative period (< or = 30 days after carotid endarterectomy), coronary events occurred in 3 patients (2%): fatal MI in 2 patients in group 4 and 1 patient in group 3. One hundred percent of patients were followed up for 6.2 years. Coronary events occurred in 23 of the 168 patients discharged from the hospital (13.7%); these were fatal in 11 (6.5%): 3 patients of group 1 (3%; sudden death in 2, fatal MI in 1), 8 patients of group 2 (29%; fatal MI in 5, unstable angina in 3), 8 patients of group 3 (28%; fatal MI in 4, nonfatal MI in 4), and 4 patients of group 4 (18%; fatal MI in 2, sudden death in 1, unstable angina in 1). Kaplan-Meier estimated curves of survival free from fatal and nonfatal coronary events were 97%, 51%, 49%, and 59%, respectively (P < .001, group 1 versus groups 2 and 3; P < .01, group 1 versus group 4). CONCLUSIONS: Among patients undergoing carotid endarterectomy, coronary events occurred twice as often as cerebral recurrences. A preoperative noninvasive cardiac investigation, including EET, can adequately identify groups of patients with diverse short- and long-term prognoses. In addition to patients with known CAD, those with silent CAD or who are unable to exercise represent, without the need of further investigation, groups at high risk of coronary events in long-term follow-up.

Adult↗