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Biomedical subjects

Alberto Balbarini

Publications and source records attributed to Alberto Balbarini.

At least 19 recordsLinked to original sources
PubMed2006

Polymorphic analysis of the matrix metalloproteinase-9 gene and susceptibility to sporadic abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) has a multifactorial aetiology and the importance of genetic components is getting increasing interest. Alteration in the structure of the vascular extracellular matrix has been described in AAA. Matrix metalloproteinases (MMPs) degrade extracellular matrix proteins which alter the vessel wall stability. We evaluated two different polymorphisms, a CA repeat and a cytosine to thymidine transition in the promoter sequence of MMP-9 gene for frequency in 146 patients with AAA. We compared the results with those of 156 healthy subjects. No difference was found in the allelic distribution of either polymorphisms. We therefore found no evidence that MMP-9 is a marker of susceptibility for AAA.

Adult↗
PubMed2006

Expression, pharmacology, and functional role of somatostatin receptor subtypes 1 and 2 in human macrophages.

Somatostatin (SRIF)-14 is recognized as an important mediator between the nervous and the immune system, although the functional role of its receptors (sst(1)-sst(5)) is poorly understood in humans. In our study, we demonstrate that human macrophages, differentiated from PBMC-derived monocytes, express sst(1) and sst(2) mRNAs. sst(1) and sst(2) are mostly localized at the cell surface and display active binding sites. In particular, sst(1)/sst(2) activation results in a weak internalization of sst(1), and the sst(2) internalization appears more efficient. At the functional level, the activation of SRIF receptors by the multiligand analogs SOM230 and KE108, but not by SRIF-14 or cortistatin-14, reduces macrophage viability. Their effects are mimicked by the selective activation of sst(1) and sst(2) using CH-275 and SMS 201-995/L-779,976, respectively. Further, sst(1)- and sst(2)-mediated effects are reversed by the sst(1) antagonist SRA-880 or the sst(2) antagonist CYN 154806, respectively. CH-275, SMS 201-995, and L-779,976, but not SRIF-14, decrease mRNA expression and secretion of the MCP-1. In addition, SRIF-14, CH-275, SMS 201-995, and L-779,976 decrease IL-8 secretion, and they do not affect IL-8 mRNA expression. In contrast, SRIF-14 and sst(1)/sst(2) agonists do not affect the secretion of matrix metalloproteinase-9. Collectively, our results suggest that the SRIF system, through sst(1) and sst(2), exerts mainly an immunosuppressive effect in human macrophages and may, therefore, represent a therapeutic window that can be exploited for the development of new strategies in pharmacological therapy of inflammation.

Amides↗
PubMed2006

Left ventricular function in normotensive young adults with well-controlled type 1 diabetes mellitus.

The aim of this study was to determine whether early myocardial structural and functional systolic and diastolic alterations in asymptomatic and uncomplicated patients with type 1 diabetes mellitus (DM) could be detected using the new highly sensitive echocardiographic techniques of integrated backscatter and color Doppler myocardial imaging. Forty asymptomatic and uncomplicated patients with type 1 DM and 40 gender- and age-matched normal controls were studied. All patients were analyzed by conventional and new echocardiographic techniques (integrated backscatter and color Doppler myocardial imaging). Patients with DM showed reduced systolic function compared with controls, evidenced by significantly lower peak strain, strain rates, and cyclic variation indexes at the septum (p <0.0001, <0.01, and <0.001, respectively) and at the posterior wall level (p <0.0001, <0.0001, and <0.001, respectively). On receiver-operating characteristic curve analysis, systolic strain and the cyclic variation index showed the highest discriminating power for separating patients with DM and control subjects. Neither structural or ultrastructural nor diastolic functional abnormalities were detected. On univariate regression analysis, a significant inverse correlation was found for DM duration with conventional (E/A ratio) and unconventional (tissue Doppler imaging E/A ratio) indexes of diastolic function, in the absence of any correlation for systolic function. In conclusion, highly sensitive ultrasonic techniques demonstrate evidence of left ventricular systolic dysfunction in the early stage of type 1 DM, in the absence of ultrastructural and left ventricular diastolic functional abnormalities.

Adult↗
PubMed2006

Obesity cardiomyopathy: is it a reality? An ultrasonic tissue characterization study.

Obesity is a well-established risk factor for congestive heart failure. Evidence has been provided indicating that insulin resistance could be the mediator between obesity and congestive heart failure, but the pathogenic mechanisms leading to myocardial alterations remain unclear. The aim of this study was to investigate, by ultrasonic integrated backscatter (IBS) analysis, subclinical alterations of left ventricular (LV) structure and function in severe obesity. Sixty consecutive, severely obese people, who were otherwise healthy (15 men, 45 women; mean age +/- SD = 31.8 +/- 7 years), were enrolled. A total of 48 sex- and age-matched nonobese healthy participants were recruited as control subjects. All participants underwent conventional 2-dimensional color Doppler echocardiography, pulsed wave Doppler tissue imaging at mitral annulus level, and IBS. The homeostasis model assessment insulin resistance index was used to assess insulin resistance; the index values in the obese group were significantly higher (mean +/- SD = 4.9 +/- 1.4) than in the control group (0.92 +/- 0.5, P < .0001). Obese patients had a greater LV mass index by height (58.5 +/- 14 g/m(2.7)) than did control subjects (37 +/- 8 g/m(2.7), P < .0001) because of compensation response to volume overload caused by a greater cardiac output (P < .02). Preload reserve was increased in obese patients, as demonstrated by the significant increase in left atrial dimension (P < .0001). This volumetric increase activated the Frank-Starling mechanism, and determined a significantly higher LV ejection fraction (P < .03) in obese patients as compared with control subjects. A slightly reduced LV diastolic function was demonstrated in obese patients (transmitral early to late peak diastolic transmitral flow velocities ratio = 1.1 +/- 0.7) as compared with control subjects (1.5 +/- 0.5, P < .02). Pulsed wave Doppler tissue imaging showed an impairment of diastolic LV longitudinal function and increased LV diastolic filling pressure. The IBS values at septum level, indexed by pericardium interface, were significantly higher for septum in the obese group (57.8 +/- 8%) than in the control group (42.3 +/- 9%, P < .0001). Additional IBS alterations were observed in the obese group, with a significantly lower cyclic variation index both at septum (P < .0001) and at posterior wall (P < .001) levels. A significant association was found between insulin resistance index and both the IBS index of myocardial reflectivity at septum level (expression of increased myocardial collagen content) or LV mass. In conclusion, this study demonstrates that obese patients exhibit myocardial structural and functional alterations related to insulin resistance and to LV volume overload, which could be considered the very early stage of incipient obesity cardiomyopathy.

Adult↗
PubMed2006

Admission C-reactive protein serum levels and survival in patients with acute myocardial infarction with persistent ST elevation.

OBJECTIVE: To evaluate the prognostic value of a single and early determination of high sensitivity C-reactive protein levels at admittance in patients with acute myocardial infarction with persistent ST elevation. PATIENTS AND METHODS: We evaluated high-sensitivity C-reactive protein levels in 247 consecutive acute myocardial infarction with persistent ST elevation patients at admittance. Patients were monitored for the occurrence of major adverse cardiovascular events. RESULTS: Mean follow-up was 26 months. High C-reactive protein levels were principally associated with age > or = 65 years (P=0.01), diabetes (P=0.03) and reduced left ventricle ejection fraction (P=0.048). We observed a significant C-reactive protein level difference between the major adverse cardiovascular event-free group and the major adverse cardiovascular event group (28.2+/-21.9 vs. 47.7+/-31.9 mg/l, P=0.03), between deceased patients group (vs. 81.5+/-51.8 mg/l, P<0.001) and early deaths (vs. 129.5+/-71.9 mg/l, P<0.001). Kaplan-Meier plots for survival and major adverse cardiovascular event occurrence showed a significant separation (P=0.01 and 0.002 by log-rank test, respectively) between high and low C-reactive protein level groups. C-reactive protein levels were independent risk predictors of major adverse cardiovascular events (odds ratio 2.931, 95% confidence interval 1.512-5.893; P=0.046) and death (odds ratio 5.068, 95% confidence interval 2.056-20.195; P=0.04). Patients with high C-reactive protein levels and age > or = 65 years were at highest risk for major adverse cardiovascular event occurrence (odds ratio 5.658, 95% confidence interval 2.898-6.249; P=0.022) and death (odds ratio 8.120, 95% confidence interval 5.656-22.729; P=0.03). CONCLUSIONS: High C-reactive protein levels identify patients with a worse prognosis after acute myocardial infarction with persistent ST elevation. The evaluation of C-reactive protein and age may provide a tool to select high-risk patients.

Aged↗
PubMed2006

Early textural and functional alterations of left ventricular myocardium in mild hypothyroidism.

The aim of the present study was to evaluate cardiac function and texture in patients with subclinical hypothyroidism (sHT) both by conventional and new ultrasonic intramyocardial tissue techniques. sHT was characterized by normal serum free tetraiodotironine and free triiodotironine levels and slightly increased serum TSH level. Twenty-four patients affected by sHT and 24 sex- and age-matched healthy volunteers were studied. All subjects were submitted to conventional two-dimensional (2D)-color Doppler echocardiography, pulsed wave tissue Doppler imaging (PWTDI) for the analysis of the diastolic function, color Doppler myocardial imaging (CDMI) for the analysis of regional strain and strain-rate and integrated backscatter (IBS) for the evaluation of intrinsic contractility and tissue characterization. The results of the present study were: (a) the detection in sHT subjects of a lower cyclic variation index (CVI) indicating an altered myocardial intrinsic contractility; (b) a higher ultrasonic myocardial reflectivity indicating an altered myocardial texture; (c) the detection of lower systolic strain and strain-rate indicating an alteration of myocardial regional deformability; (d) an initial impairment of left ventricular diastolic function indicated by a decrease of peak E mitral flow velocity and an increase of peak A mitral flow velocity. All parameters studied with conventional 2D-echo in sHT patients were comparable with controls, except for a mild alteration in diastolic function. A significant correlation among systo-diastolic modifications detected by CDMI and IBS and serum TSH levels were found. The CVI at septum, the PWDTI S-peak wave and the systolic strain at septum were inversely related to the serum TSH levels. In conclusion, the new intramyocardial ultrasonic techniques confirm and extend the previous knowledge on the effect of the sHT on the heart, allowing the detection of early ultrastructural and regional functional systolic and diastolic abnormalities.

Adult↗
PubMed2006

A case of acute myocardial infarction during 5-fluorouracil infusion.

Cardiac toxicity is an uncommon side-effect of 5-fluorouracil (5-FU) treatment, consisting mainly of chest pain episodes with or without electrocardiographic changes and dysrhythmias. Here, we describe the case of a 56-year-old male patient with a diagnosis of advanced colorectal cancer who developed an acute myocardial infarction during 5-FU infusion. The patient was not affected by prior heart disease and did not show any classic risk factors for coronary heart disease. Coronary angiography examination revealed no evidence of coronary stenosis, supporting the hypothesis of a coronary artery spasm related to 5-FU infusion. Given the great number of cancer patients receiving 5-FU containing chemotherapeutic regimens, this rare but severe cardiac side-effect may be observed in both cardiologic and oncologic clinical practice. We suggest a tight clinical monitoring of all patients receiving 5-FU infusions, even in those without a prior history of heart disease.

Antimetabolites, Antineoplastic↗
PubMed2006

[Medical therapy in critical lower limb ischemia when immediate revascularization is not feasible].

Revascularization by either bypass surgery or endovascular recanalization is considered the first-choice treatment in patients with critical limb ischemia (CLI). Only conservative options are left in CLI patients in whom successful revascularization strategies are not possible: in these patients, at present, prostanoids (iloprost and prostaglandin [PGE1]) represent the pharmacological treatment of choice. Iloprost resulted more effective than PGE1, in a 6 month follow-up, in both limb savage and in prevention of cardiovascolar death, either in diabetic or non diabetic patients with unreconstructable CLI. In our experience, in patients who have responded to a first cycle of therapy (early responders), performed for at least 2-3 weeks, cyclic annual further treatments with iloprost are usually able to stabilize arterial disease, with a regression to Fontaine II stage and, in absence of further arterial complications, with complete limb preservation for an unlimited period of time. In non-responder patients, who are not urgently supposed to undergo amputation, a second cycle of iloprost carried out within few months from the first one, is able to increase the percentage of responders to prostanoids (late responders). Vice versa, in non-responders to repeat prostanoid cycles, it is useful to verify the outcomes of further attempts at saving, the symptomatic limb by surgical or endovascular re-timing, spinal cord stimulation, gene or stem cell therapy. Our recent better outcomes are related to earlier microvascular diagnosis and to earlier, repeat, pharmacological treatments with iloprost. Transcutaneous oxygen and carbon dioxide monitoring improves the possibility of an earlier diagnosis of microvascular damages and categorizes CLI patients in responders and non-responders after prostanoid treatments.

Adolescent↗
PubMed2005

New-onset ventricular tachycardia after cardiac resynchronization therapy.

It is well established that coronary artery disease with healed myocardial infarction is the most common backdrop for ventricular tachycardia (VT). Although the clinical benefits of biventricular pacing (BivP) in the treatment of severe heart failure are well documented, exact relation with ventricular arrhythmias remains still unclear. We describe a case of a patient, whitout a previous history of arrhythmic episodes, in which the onset of several episodes of VT presented immediatly after cardiac resynchronization therapy (CRT) and did not occur after BivP discontinuation.

Cardiac Pacing, Artificial↗
PubMed2005

Distal embolization during primary angioplasty: histopathologic features and predictability.

BACKGROUND: Distal embolization during primary percutaneous coronary interventions (PCIs) may affect myocardial reperfusion. We evaluated the prevalence and features of embolization during primary PCI and its relationship with clinical and angiographic variables. METHODS: Forty-six consecutive patients with acute myocardial infarction underwent primary PCI with a filter-based distal protection device. Histopathologic analysis was performed on retrieved embolic fragments, assessing the presence and relative amount of fibrin, necrosis, lipid droplets, collagen, mucopolysaccharides, and leukocytes, as well as the total debris volume. Such variables were related to baseline clinical and angiographic variables. RESULTS: Embolic material was recovered in 41 (89%) of 46 cases, with a mean total debris volume of 1.2 +/- 2.2 mm3. Prevalent histopathologic patterns were organized thrombus (47%), fresh thrombus (29%), and plaque fragments (24%). At multivariate analysis, none of the baseline clinical variables considered significantly predicted the total debris volume. Among angiographic variables, angiographic signs of high thrombus burden (cut-off coronary occlusion pattern or large intracoronary minus image) independently predicted the total debris volume at multivariate analysis (odds ratio 15.8, P < .005). Compared with its nonuse, abciximab did not affect the total number and the mean total volume of embolized material (15 +/- 16 vs 10 +/- 8 fragments, 1.5 +/- 2.5 vs 1.0 +/- 1.9 mm3, respectively, for both P > .20), or its qualitative composition. CONCLUSIONS: Distal embolization occurs in most patients during primary PCI and mainly consists of plaque fragments and partially organized thrombi, which are likely to be scarcely responsive to antiplatelet drugs. Baseline angiographic signs of a high thrombus burden are the only significant predictors of the extent of distal embolization.

Angioplasty↗
PubMed2004

Allelic genes involved in artery compliance and susceptibility to sporadic abdominal aortic aneurysm.

Vascular smooth muscle cells (VSMCs) synthesize elastin (ELN), major protein of aortic tunica media which confers strength and elasticity to aortic wall. Protein loss or distortion is typical in aneurysm tunica media. Transforming growth factor beta1 (TGFbeta1) inhibits growth and connective protein expression of abdominal VSMCs cultures. Also, in atherogenic studies, estrogen (but not estrogen plus progestin) treatments inhibit aortic collagen accumulation and elastic loss, risk factors to subsequent aortic enlargement. Therefore, polymorphisms of ELN, estrogen receptor alpha (ERalpha) and beta (ERbeta), progesterone receptor (PR) and TGFbeta1 genes and their products may be involved in the abdominal aortic aneurysm (AAA) development. Using PCR-RFLP method, we analyzed ELN RmaI (exon 16), ERalphaPvuII-XbaI (intron 1), ERbetaAluI (exon 8), PR TaqI (intron 7) and TGFbeta1 Bsu36I (-509 bp, promoter) polymorphisms in 324 Caucasian male subjects: 225 healthy controls (mean age 71.20 +/- 6.85 years) and 99 unrelated AAA patients (mean age 69.8 +/- 7.1 years). No difference in ELN, ERalpha, PR and TGFbeta1 allele frequencies was observed in AAA patients versus controls (P > 0.05). However, because possessing at least an ERbetaAluI restriction site was statistically associated to AAA onset (chi(2) = 5.220; OR = 1.82, P < 0.05), ERbeta polymorphism was proposed as genetic determinant in the AAA susceptibility.

Aged↗
PubMed2004

Passive smoking and coronary heart disease.

A large series of clinico-epidemiological studies, meta-analyses and experimental findings have concluded that there is a relationship between coronary heart disease (CHD) and passive smoking either after acute or chronic exposure. Cigarette smoking is the most important cause of premature death in industrialized countries because it is associated with an increased risk of developing several types of cancer and arterial disease. In family homes as well as in workplaces, environmental tobacco smoke (ETS) exposure is associated with an increased risk of CHD in exposed non-smokers when compared to un-exposed non-smokers. Different anatomical structures are damaged by ETS. The endothelium, artery wall and heart are target organs for passive smoking. Therefore, smoking cessation will benefit both smokers and those exposed to ETS.

Cohort Studies↗
PubMed2004

[Therapeutic angiogenesis of critical lower limb ischemia. Review of the literature and prospects of research on stem cells].

Chronic peripheral arterial disease affects up to 15% of adults over the age of 55 years; critical limb ischemia represents the most dramatic clinical outcome. Patients with chronic critical limb ischemia who are not candidate for surgical or percutaneous revascularization have impending limb loss; those who benefit from successful revascularization suffer from high rate of recurrent symptoms or revision surgery or progressive amputations. In these patients no medical treatment is considered effective for rest pain or ulcer healing. Therapeutic angiogenesis, which has the goal to achieve the process of new blood vessel formation via the administration of growth factors, has become a new promising hope. The discovery of the possibility of inducing sprouting of new vessels from preexisting vasa (angiogenesis) or the in situ differentiation of endothelial cells from stem cell precursors (vasculogenesis) have open new lease on life. However, a careful analysis of experimental results achieved in animal models is required before proposing for clinical setting. Although a major concern is that most of the experimental work has been done on animal models that do not represent the clinical process, benefit from growth factor administration or stem cell therapy has been proven in clinical trials, suggesting the importance of this new research frontier. This literature review is aimed to examine potential applications of therapeutic angiogenesis to treat critical limb ischemia with particular attention to angiogenesis obtained with stem cells.

Animals↗
PubMed2004

[Major and minor amputation rates and lower critical limb ischemia: the epidemiological data of western Tuscany].

BACKGROUND: The aim of this study was to evaluate the incidence of major amputations and critical limb ischemia in an unselected population of western Tuscany. METHODS: Out of an overall 1234000 people living in Pisa and surroundings (western Tuscany), a total amount of 306 patients underwent 319 different major/minor amputations during the year 2002 in private and public hospitals, both in Tuscany and in other regions. RESULTS: 84.6% (n = 270) of the amputations were atherosclerotic, while 15.4% (n = 49) were non-atherosclerotic. The patients with unreconstructable critical limb ischemia, who underwent amputations at the symptomatic limbs, had a minor amputation rate (at toes or forefoot) of 46.7%, while the major amputation rate (over the ankle) was 53.3%. The 144 major amputations were performed in 76.4% (n = 110) of the cases above the knee and in the remaining 23.6% (n = 34) of cases below the knee. Early hospital mortality rates of the amputees for ischemic causes were 7.6% in patients who underwent major amputations, and 0.8% in cases with minor amputations, respectively. Overall, in western Tuscany, the incidence of the major amputation rate per million inhabitants was 117 cases per year, with a total of 468 new cases of reconstructable and unreconstructable critical limb ischemia per year (this number was calculated multiplying by 4 the number of major amputations). CONCLUSIONS: On the basis of our real epidemiological data, the theoretical major amputation rates per year were 408 in Tuscany and 6652 in Italy, respectively. The extrapolation of our results showed that the overall critical limb ischemia incidence consists of 1638 cases in Tuscany and of 26676 patients in Italy, respectively.

Adolescent↗
PubMed2003

Heterogeneous effect of calcium antagonists on leg oedema: a comparison of amlodipine versus lercanidipine in hypertensive patients.

AIMS: To compare the effect of amlodipine, a prototype dihydropyridine calcium-channel blocker with lercanidipine, a newer dihydropyridine compound with lipophilic properties, on dependent oedema generation and interference with skin blood flow vasomotion in hypertensive patients. DESIGN: Single-blind, sequence-randomized, cross-over comparison of amlodipine and lercanidipine. Drugs were given at equipotent doses (10 mg daily and 20 mg daily, respectively) in 22 never-treated mild-to-moderate hypertensive men (age: 48 +/- 5 years). Each treatment was administered for 2 weeks with a 2-week intervening period to restore baseline values. MAIN OUTCOME MEASURES: Dependent oedema formation was quantified through leg weight changes (water displacement method). Blood pressure (the mean of at least 10 determinations) was recorded by an automated oscillometric device and skin blood flow (laser Doppler flowmetry) measured at the dorsum of the foot, both supine and with the limb passively placed 50 cm below the heart level, to evaluate the behaviour of cutaneous postural vasoconstriction, an autoregulatory mechanism that minimizes gravitational increases in capillary pressure and avoids fluid extravasation when standing. RESULTS: Leg weight was increased by both drugs, but the increase was significantly greater during treatment with amlodipine than with lercanidipine. Blood pressure decreased to a similar extent and postural vasoconstriction was antagonized comparably during both treatments. CONCLUSIONS: The oedema-forming potential of amlodipine is greater than that induced by lercanidipine, a difference which emerged in the presence of a comparable drop in blood pressure and could not be attributed to interference with postural vasoconstrictor mechanisms.

Adult↗