Biomedical subjects
Publications and source records attributed to F Romeo.
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BACKGROUND: Computed tomography has been shown to be useful in the evaluation of aortocoronary bypass grafts (CABG). This is the first prospective study to evaluate the accuracy of a new-generation scanner in the detection of patency and significant stenoses (>50% decrease in diameter) of venous and arterial grafts in patients with previous CABG. METHODS AND RESULTS: In 96 patients (80 males, mean age 62 years) with previous CABG, a multislice computed tomography (MSCT) scan was performed (collimation 16x0.625 mm). Patients with atrial fibrillation, renal failure, severe respiratory disease, severe heart failure, heart rate >70 bpm despite therapy, or unstable angina were excluded. A total of 285 conduits implanted on the native coronary arteries at the time of CABG were evaluated. MSCT data were analyzed by 2 independent radiologists and compared with the results of conventional angiography. Three patients were excluded from analysis. All conduits were judged evaluable in 84 patients. Among these patients, MSCT correctly diagnosed 54 occluded grafts and 4 significant stenoses on the body of the grafts. Of the 17 significant anastomotic lesions, MSCT correctly diagnosed 15. For these 84 patients, diagnostic accuracy was 99%, sensitivity was 97%, and specificity was 100%. When all 93 patients were considered, the sensitivity of MSCT in diagnosing significant stenoses was 96%. CONCLUSIONS: MSCT with the new-generation scanner allows for accurate assessment of venous and arterial conduits in patients with previous CABG with a high degree of sensitivity and specificity. Exclusion criteria and radiation exposure remain limitations of the method.
Abstract Cytochrome P450 aromatase is a terminal enzyme that catalyses the conversion of androgens into oestrogens. This study investigated the immunohistochemical localization of aromatase in human efferent ductules and proximal ductus epididymis using a mouse anti-human monoclonal P450arom IgG as primary antibody and a goat anti-mouse biotinylated IgG as secondary antibody. A strong immunoreaction was observed in the epithelial cell cytoplasm of both ductuli efferentes and proximal ductus epididymis, whereas the smooth muscle cells were immunonegative in the two regions. The results show, for the first time in humans, that epithelial cells of ductuli efferentes and proximal caput epididymis express aromatase, suggesting that locally produced oestrogens may have a role in epididymal function.
Atrial fibrillation is the most common cardiac arrhythmia and the most frequent cause of hospitalization and utilization expense among all heart diseases. Taking into account persistent atrial fibrillation we know that, in order to cardiovert persistent atrial fibrillation, external direct current cardioversion is the method most frequently used to restore sinus rhythm. But external cardioversion has also some limitations: it requires high energy direct current shocks so that patients have to be anaesthetised, which means a dedicated apparatus and place to adequately assist the patients. The oesophageal cardioversion is an alternative method to restore sinus rhythm, which could obviate some of these limitations of external cardioversion. Compared to external cardioversion oesophageal one has lower defibrillation impedance and requires lower energies to restore sinus rhythm, increasing for the same energy level, success rate. Using low energy shocks, a mild sedation is sufficient to make the procedure well tolerated by most of patients. Other 2 important advantages coming from low energy shocks are the safety in patients with pacemaker or implantable cardioverter-defibrillator and the availability of a back up atrial pacing. Oesophageal cardioversion is not indeed a new technique. Looking at literature, studies in animals and in humans have been performed since the 60s, assessing feasibility, effectiveness and safety of such a procedure. The oesophageal-precordial cardioversion is usually performed on an outpatient regimen, resulting in a very cost-effective method to cardiovert patients with persistent atrial fibrillation, which may definitely represent a real alternative technique to external cardioversion.
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LOX-1, a receptor for oxidized low-density lipoprotein (ox-LDL), plays a critical role in endothelial dysfunction and atherosclerosis; both of these conditions are associated with diminished expression of constitutive endothelial nitric oxide synthase (eNOS). Recent studies show that HMG CoA reductase inhibitors (statins) exert cardioprotective effect. We examined the role of LOX-1 in eNOS expression and modulation of this relationship by two different statins, simvastatin and atorvastatin in human coronary artery endothelial cells (HCAECs). Ox-LDL (40 microg/ml) upregulated the expression of LOX-1; simultaneously, there was a reduction in eNOS expression. Pretreatment of HCAECs with simvastatin or atorvastatin (1 and 10 microM) reduced ox-LDL-induced upregulation of LOX-1 and downregulation of eNOS (both P < 0.05). High concentration of statins (10 microM) was more potent than the low concentration (1 microM) (P < 0.05). Both statins also attenuated ox-LDL-mediated activation of MAP kinase. These observations indicate that statins attenuate the effect of ox-LDL on eNOS expression. Inhibitory effect on LOX-1 and subsequently MAP kinase activity provides a potential mechanism of beneficial effects of statins beyond lowering cholesterol.
BACKGROUND: alpha-Tocopherol has received much attention in the primary and secondary prevention of coronary artery disease. Absence of other isoforms, such as gamma- and delta-tocopherol, in commercial preparations of vitamin E may account for the inconsistent results of clinical trials. Since platelet aggregation is intimately involved in thrombogenesis, the relative effects of alpha-, gamma-, and delta-tocopherol and their combination were examined on human platelet aggregation, lipid peroxidation, and constitutive nitric oxide synthase (cNOS) activity. METHODS AND RESULTS: Human platelets were incubated with the three different isoforms of tocopherol and their combination for 30 minutes, and then ADP-induced platelet aggregation measured. All three isoforms of tocopherol markedly and similarly decreased platelet aggregation in a concentration (120--480 microM)-dependent manner. All three tocopherols also decreased the level of the lipid peroxidation product, malondialdehyde (MDA), and increased NO release (P < 0.05 vs control). These isoforms of tocopherol did not affect cNOS protein expression, but enhanced cNOS phosphorylation in platelets. The combination of three tocopherols in a concentration found in nature was more potent than alpha-, gamma-, or delta-tocopherol alone in this regard. CONCLUSION: These observations suggest that all three major isoforms of tocopherol have a similar effect on human platelet aggregation. The three isoforms appear to attenuate platelet aggregation at least in part via a decrease in free radical generation and an increase in platelet cNOS activity. The combination of tocopherols has a synergistic platelet inhibitory effect. Future clinical trials should concentrate on the combination of these three isoforms of tocopherols.
BACKGROUND: We evaluated the occurrence of a rapid process of restenosis after percutaneous mitral valvuloplasty (PMV), initiated by the recurrence of acute rheumatic fever. Restenosis after PMV has been mainly related to a high echocardiographic score (> or = 8) indicating a severely compromised mitral valve apparatus. METHODS: From 1986 to 1996, 120 patients underwent PMV by the transseptal approach at our Institution. The mean follow-up time was 58 +/- 32 months (range 3 months to 9 years). RESULTS: Restenosis occurred in 10 patients (8.3%): in 4 restenosis was found within a relatively short period of time (1 to 3 months) following a documented recurrence of acute rheumatic fever; in the other 6 patients there was a gradual loss of the initial gain in the mitral valve area. CONCLUSIONS: These data suggest two potential mechanisms of restenosis: 1) a more common slow process, due to turbulent flow-trauma on the mitral valve; 2) a rapid process that relates to valvulitis consequent to a recurrence of acute rheumatic fever. In consideration of the second possibility, after PMV prophylactic treatment may be warranted at least in those patients who are at high risk of streptococcal infection.
BACKGROUND: We demonstrated earlier that angiotensin II (Ang II), by AT(1) receptor activation, upregulates oxidized LDL (ox-LDL) endothelial receptor LOX-1 gene expression and uptake of ox-LDL in human coronary artery endothelial cells (HCAECs). In this study, we investigated the regulation of Ang II receptors (AT1R and AT2R) by ox-LDL and the role of the redox-sensitive transcription factor NF-kappaB in this process. METHODS AND RESULTS: HCAECs were incubated with ox-LDL for 24 hours. Ox-LDL (10 to 40 microg protein/mL) upregulated AT1R but not AT2R, mRNA, or protein. Ox-LDL degraded IkappaBalpha in cytoplasm and activated transcription factor NF-kappaB (P65) in HCAEC nuclear extract. Treatment of cells with the antioxidant alpha-tocopherol (10 to 50 micromol/L) attenuated ox-LDL-mediated degradation of IkappaBalpha and activation of NF-kappaB (P65) and inhibited the upregulation of AT1R mRNA and protein. The role of NF-kappaB signal transduction was further examined by use of an NF-kappaB inhibitor, caffeic acid phenethyl ester (CAPE). Pretreatment of cells with CAPE inhibited ox-LDL-mediated degradation of IkappaBalpha and NF-kappaB activation and inhibited ox-LDL-induced upregulation of AT1R expression. Incubation of cells with both ox-LDL and Ang II increased cell injury, measured as cell viability and LDH release, compared with either ox-LDL or Ang II alone. alpha-Tocopherol as well as the specific AT1R blocker CV11974 (candesartan) attenuated the cell-injurious effects of ox-LDL. CONCLUSIONS: These observations suggest an important role of ox-LDL-mediated AT1R upregulation in cell injury. In this process, NF-kappaB activation seems to play a critical role in signal transduction. These findings provide a basis for the use of antioxidants and AT1R blockers in designing therapy of atherosclerosis.
BACKGROUND: Results of therapy in patients with unstable coronary syndromes with antibiotics directed against Chlamydia pneumoniae have been variable, perhaps due to the heterogeneity of patients in these trials. HYPOTHESIS: The aim of the present study was to correlate the severity of coronary artery disease (CAD) with seropositivity against C. pneumoniae prospectively. METHODS: We measured the frequency of seropositivity (IgG levels > or = 1/64 and IgA levels > or = 1/16 against Chlamydia pneumoniae) in 110 patients with CAD and in 49 controls. RESULTS: As expected, traditional CAD risk factors were seen more often in patients with CAD than in controls. Mean values of total cholesterol (184 +/- 52 and 166 +/- 44 mg/dl, respectively) and triglyceride (143 +/- 60 and 112 +/- 63 mg/dl, respectively) in serum were significantly higher in patients with CAD than in controls (both p < 0.04). There were no significant differences between the two groups in serum high-density lipoprotein cholesterol (34 +/- 13 and 32 +/- 14 mg/dl, respectively) and lipoprotein (a) (Lp(a):241 +/- 247 and 223 +/- 263 mg/l, respectively) levels. The rate of IgG seropositivity was 52% (28/54) in patients with stable CAD, 41% (23/56) in patients with unstable CAD, and 35% in controls (p = NS). The rate of IgA seropositivity was 25% (14/54) in patients with stable CAD, 12% (6/49) in patients with unstable angina, and 12% (6/49) in controls (all p = NS). CONCLUSIONS: Only a small percentage of patients with CAD demonstrate seropositivity against Chlamydia pneumoniae. Antibiotic therapy in these selected patients, but not in the remaining patients, may be considered rational. These considerations may underlie the failure to see consistent benefits of antibiotic therapy in patients with CAD.
BACKGROUND: Several studies have shown that carvedilol, a multiple action neurohumoral antagonist, reduces mortality in patients with congestive heart failure (CHF). In addition to being a beta-adrenoceptor antagonist, carvedilol is a potent antioxidant. Since there is evidence for elevation of catecholamine levels in plasma and coronary artery endothelial cell injury in CHF, the present study was designed to test the hypothesis that carvedilol inhibits epinephrine-induced apoptosis, and the inhibitory effect is mediated by modulation of Fas, Fas ligand (FasL) and caspase-3 pathway, in cultured human coronary artery endothelial cells (HCAECs). METHODS AND RESULTS: HCAECs were exposed to epinephrine alone, carvedilol + epinephrine, or atenolol + epinephrine for 24 h. Epinephrine increased the number of apoptotic cells, measured by in situ nick end-labeling staining (from 4.2 +/- 1.3% to 28.6 +/- 6.0%, P < 0.01, n = 6) and by DNA laddering on agarose gel electrophoresis. Epinephrine also increased Fas and FasL protein expression (P < 0.01 vs. control, n = 6), and activated intracellular protease caspase-3 (P < 0.01 vs. control, n = 6). These effects of epinephrine were completely inhibited by carvedilol. Atenolol in equimolar concentration also attenuated epinephrine-mediated effects, but the effects of atenolol were less marked than those of carvedilol (P < 0.01). To explore the basis of differential effects of carvedilol and atenolol, effects of these agents on epinephrine-induced lipid peroxidation was measured. Lipid peroxidation was completely blocked by carvedilol, whereas equimolar concentration of atenolol had much less (P < 0.05) effect. CONCLUSION: Epinephrine induces apoptosis in HCAECs, and this effect is associated with activation of Fas-FasL and caspase-3 signal transduction pathway. Carvedilol can, more effectively than atenolol, inhibit these effects of epinephrine. The potent antioxidant effect of carvedilol is probably responsible for the superior effect.
Since the recent publication of 3 studies on the use of antibacterials in patients with coronary artery disease (CAD), there has been a phenomenal interest in the role of infection in the genesis of CAD. It is now generally accepted that inflammation accompanies atherosclerosis from its initiation to the evolution of end-events. Inflammation may occur in response to traditional risk factors, such as hyperlipidaemia, smoking and diabetes mellitus. There is a recent resurgence of the concept that inflammation may have an infectious basis. This concept is based on the identification of microorganisms in the atherosclerotic plaque and seropositivity. The data on eradication of the offending organism with antibiotics and prevention of atherosclerosis-related events have, however, been inconsistent. This may reflect lack of precise understanding of steps leading to atherosclerosis and the evolution of acute ischaemic events. Further work in this area may help identify subsets of patient populations within which infection may play a causative role in the genesis of CAD. Targeted therapy then may be considered logical.
Woven coronary malformation is characterized by the branching of a major epicardial coronary artery into thin channels which then merge again in a normal conduit. The angiogram can suggest a filling defect instead of a malformation and an undue coronary angioplasty could be performed determining some damage to the arterial wall. In this case report we describe a patient with a stenosis on the left anterior descending coronary artery and a woven coronary artery on the right coronary artery. In 1995 a coronary angioplasty was performed on the left anterior descending coronary artery. Four years later a coronary angiogram did not show any changes in the right coronary artery. In this patient the malformation did not induce any reduction in the coronary reserve as shown at cardiac scintigraphy. We need more information about the natural history of such a malformation.
BACKGROUND: Increasing evidence suggests that vitamin E prevents the progression of atherosclerosis by inhibiting platelet aggregation, monocyte adhesion, and improving plaque stability and vasomotor function. Recently, controversy has arisen as to the relative effects of alpha- and gamma-tocopherol in modulating some mediators of atherosclerosis. METHODS AND RESULTS: We examined the effects of alpha- and gamma-tocopherol on constitutive nitric oxide synthase (cNOS) and superoxide dismutase (SOD) activity and protein expression in rats. Sprague-Dawley rats were fed regular chow or chow mixed with alpha- or gamma-tocopherol (100 mg/kg/day) for 7 to 10 days. Plasma alpha- and gamma-tocopherol levels, low-density lipoprotein (LDL) oxidation, and cNOS and SOD activity and protein expression were measured. Plasma alpha-tocopherol levels were significantly increased (eP <.01 vs control), but gamma-tocopherol levels fell (P <.01 vs control) in rats fed alpha-tocopherol. Plasma gamma-tocopherol levels were increased (P <.01 vs control), and alpha-tocopherol levels did not change in rats fed gamma-tocopherol. Both alpha- and gamma-tocopherol feeding decreased the rate of LDL oxidation induced by phorbol 12-myristate 13-acetate (PMA)-stimulated leukocytes (P <.01 vs control). Both alpha- and gamma-tocopherol increased SOD activity in plasma and arterial tissues as well as Mn SOD and Cu/Zn SOD protein expression in arterial tissues (all P <.01 vs control). gamma-Tocopherol was more potent than alpha-tocopherol in all these effects (P <.05). Both a- and gamma-tocopherol increased NO generation and cNOS activity (all P <.05 vs control). However, only gamma-tocopherol increased cNOS protein expression. CONCLUSIONS: These observations indicate that whereas both alpha- and gamma-tocopherol exert important effects on determinants of oxidationand vasomotor function, effects of dietary gamma-tocopherol supplementation in vivo are less pronounced than those of gamma-tocopherol supplementation.
PURPOSE: To evaluate the activity and toxicity of the combination of cisplatin (80 mg/m2 day 1) and vinorelbine (25 mg/m2 days 1 and 8) in patients with carcinoma of the uterine cervix that has not been previously treated with chemotherapy. PATIENTS AND METHODS: Fifty patients with cervical cancer were enrolled onto this study (27 stage IB-III, 23 stage IVB-recurrent). A two-stage optimal Simon design was applied. Thirteen responders of 29 treated patients were required to proceed beyond the first stage, and 28 responders were needed overall. RESULTS: Hematologic toxicity was mild, with neutropenia being the most frequent side effect. Nonhematologic toxicity was frequent but never severe; one patient had grade 3 peripheral neurotoxicity. Objective responses were recorded for 32 patients (64%): 11 patients (22%) achieved a complete response (CR) and 21 patients (42%) achieved a partial response (PR). The response rate was 81.5% in patients with IB-III stage (25.9% CR rate) and 43.5% in patients with IVB-recurrent disease (17.4% CR rate). Responses were seen both in stage IVB patients (one CR and two PRs, for an overall rate of 37.5%) and in patients with recurrent disease (three CRs + four PRs, for an overall rate of 46.7%). CONCLUSION: The combination of cisplatin and vinorelbine is an active regimen in the treatment of patients with early-stage and advanced carcinoma of the uterine cervix. The hematologic and nonhematologic toxicity of this combination is mild.
To assess the diagnostic and medicolegal contribution of Computed Tomography (CT) in patients with craniocerebral, maxillofacial, neck and spine gunshot wounds, we submitted to CT 106 patients with gunshot wounds examined over a 7-year period (February, 1988 to December, 1994). Twenty-four of them had craniocerebral injuries (23%), 9 maxillofacial (8%), 8 neck (8%) and 10 vertebral (9%) injuries. Emergency CT demonstrated the mechanism of the injury, the bullet path and site, the site of bone and/or metallic fragments, and damage extent. In all perforating cranioencephalic injuries (n = 7) intracerebral or extrathecal bone fragments were demonstrated adjacent to the bullet entrance and exit holes, respectively. In injury monitoring. CT showed injury evolution, retained fragments and complications, thus enabling damage extent assessment. High Resolution Computed Tomography (HRCT) was useful in locating minute orbitary retrobulbar and intraspinal fragments. Magnetic Resonance (MR) Imaging in postoperative patients proved a valuable tool to assess the extent of spinal cord damage. To conclude, CT is a useful technique to examine the patients with gunshot wounds, which helps plan adequate treatment and solve complex medicolegal problems.
The aim of this study was to evaluate the impact of concurrent nitroglycerin administration on the thrombolytic efficacy of recombinant tissue-type plasminogen activator (rTPA) in patients with acute anterior myocardial infarction (AMI). Sixty patients (53 men, 7 women; mean age 54 +/- 7 years) with AMI entered the study. Thirty-three patients were randomized to receive rTPA alone (100 mg in 3 hours) (group A) and 27 to receive rTPA plus nitroglycerin (100 micrograms/min) (group B). Time from the onset of chest pain and delivery of rTPA was similar in the two groups of patients. Patients in group A had signs of reperfusion more often than the patients in group B (25 of 33 or 75.7% vs 15 of 27 or 55.5%, p < 0.05). Time to reperfusion was also shorter in group A than in group B (19.6 +/- 9.4 minutes vs 37.8 +/- 5.9 minutes, p < 0.05). Group B had a greater incidence of in-hospital adverse events (9 of 27 vs 5 of 33, p < 0.05) and a higher incidence of coronary artery reocclusion (8 of 15 or 53.3% vs 6 of 25 or 24%, p < 0.05). Peak plasma levels of rTPA antigen were higher in group A compared with group B (1427 +/- 679 vs 512 +/- 312 ng/ml, p < 0.01). In conclusion, concurrent nitroglycerin administration reduces the thrombolytic efficacy of rTPA in patients with AMI probably by lowering the plasma levels of rTPA antigen. The diminished efficacy of rTPA is associated with an adverse outcome.
OBJECTIVES: The aim of the present study was to evaluate the effectiveness of prolonged administration of thrombolytic therapy with low doses of recombinant tissue-type plasminogen activator (rt-PA) in patients with refractory unstable angina. BACKGROUND: Intracoronary thrombosis is often the cause of instability in patients with unstable angina. Thrombolytic therapy has been tested in these patients with conflicting results. METHODS: Sixty-seven patients with unstable angina refractory to standard antianginal therapy were randomized to receive, in addition to the common antianginal therapy, either rt-PA (0.03 mg/kg body weight per h for 3 consecutive days) plus heparin (to achieve activated clotting time of 250 to 400 s) (36 patients, group A) or the same dose of heparin plus placebo (31 patients, group B). RESULTS: No major bleeding was observed in either group of patients. One patient in group A and four in group B (2.7% vs. 12.9%, p < 0.01) developed acute myocardial infarction during the hospital period. Eight patients in group B underwent emergency coronary artery surgery or angioplasty because of worsening of symptoms. Group A patients had a significant reduction in the occurrence of chest pain compared with those in group B (95% confidence interval -7.2 to -2.1 episodes/3 days, p < 0.01). Patients in group B had a greater number of episodes of transient myocardial ischemia (237 vs. 103, p < 0.01) and a longer total ischemic burden (114 +/- 23 vs. 45.6 +/- 8.9 min/day, p < 0.01) than group A patients. After a mean follow-up of 14 +/- 6 months, group A patients were more frequently angina free and had a lower incidence of readmission to the hospital than group B patients. CONCLUSIONS: The combination of heparin and protracted administration of rt-PA at low doses is effective in stabilizing and reducing in-hospital adverse events in patients with unstable angina refractory to antianginal therapy.