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Biomedical subjects

A Angelini

Publications and source records attributed to A Angelini.

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

Local photodynamic therapy with Zn(II)-phthalocyanine in an experimental model of intimal hyperplasia.

Photodynamic therapy (PDT) appears to be a novel promising modality to prevent intimal hyperplasia (IH) and restenosis after angioplasty. Local PDT, that consists of local delivery of photosensitizing agents followed by intraluminal local irradiation, represents a recent advancement. This methodology requires optimization in order to achieve the best prompt outcome especially in terms of pharmacokinetics of the photosensitizing agent. We studied the pharmacokinetic properties by using the photosensitizing agent Zn(II)-phthalocyanine (ZnPc), locally released by a channeled balloon. The efficacy of local PDT in reducing IH was evaluated in an experimental rabbit model of arterial injury. The maximum accumulation of ZnPc was found at 30 min: the injured portion of the artery gave a ZnPc recovery of 1.18 micromol/mg, as compared with undetectable amounts of ZnPc in the non injured arteries; within 90 min after the local delivery, clearance of the agent was almost complete. Local PDT produced an effective reduction of IH in our vascular injury model: at 7, 14, 21 and 28 days IH and intima/media ratio (IMR) was significantly reduced as compared with balloon injured arteries. The local delivery of ZnPc showed favourable pharmacokinetic properties, that allow the performance of PDT immediately after the vascular injury. Local PDT performed in these conditions represents a promising approach to prevent IH after balloon injury. Further studies are needed to better clarify the biological response of the injured arterial wall to local PDT.

Animals↗
PubMed2000

Sulfinpyrazone reduces cyclosporine levels: a new drug interaction in heart transplant recipients.

BACKGROUND: Management of cyclosporine (CsA)-associated hyperuricemia in heart transplantation (HT) is difficult. Because of the myelotoxicity of combined allopurinol and azathioprine, we tested sulfinpyrazone. METHODS: We studied 120 HT recipients (109 men; mean age at HT, 52+/-10 years). All had received allopurinol for at least 6 months, which was stopped for 1 month before initiation of sulfinpyrazone. Mean follow-up from HT to onset of sulfinpyrazone (200 mg/day) was 59+/-41 months. We stopped the drug after 6+/-2 months. We compared CsA level and daily dose, serum creatinine, blood urea, and uric acid at onset and before interruption of sulfinpyrazone and, as control, in the last 6 months of allopurinol. RESULTS: Mean uricemia decreased with allopurinol (0.58+/-0.12 vs. 0.41+/-0.07 mmol/liter, p = 0.0001) as well as with sulfinpyrazone (0.51+/-0.13 vs. 0.40+/-0.12 mmol/liter, p = 0.0001). Mean creatinine increased (171+/-42 and 164+/-35 micromol/liter, p = 0.01) with allopurinol, whereas it tended to decrease with sulfinpyrazone (160+/-35 and 154+/-48 micromol/liter, p = NS). Mean urea did not change with allopurinol (14+/-5 vs. 15+/-7 mmol/liter, p = NS), but fell with sulfinpyrazone (14.01+/-5 vs. 12.60 +/-5 mmol/liter, p = 0.0004). Mean CsA levels were constant with allopurinol (193+/-73 vs. 188+/-65 ng/ml, p = NS), although CsA dose was slightly reduced (2.7+/-0.8 vs. 2.6+/-0.8 mg/kg/day, p = 0.007). Conversely, CsA levels dropped with sulfinpyrazone (183+/-89 vs. 121 +/-63 ng/ml, p = 0.0001) despite an increase in CsA daily dose (2.6 +/-0.9 vs. 2.8+/-0.9 mg/kg/day, p = 0.0001). Two subjects were treated for acute rejection. We observed no other side effects. In HT recipients sulfinpyrazone, as an alternative to allopurinol, is effective in achieving metabolic control of hyperuricemia. However, this drug reduced CsA levels, thus the risk of rejection is present.

Allopurinol↗
PubMed2000

Morphological aspects of Ebstein's anomaly in adults.

The essence of the Ebstein's malformation is that the tricuspid valve leaflets do not attach normally to the valve annulus, and the effective orifice is displaced downward into the right ventricular cavity at the junction of the inlet and trabecular components of the right ventricle. Only the septal and posterior leaflets are displaced and divide the right ventricle into two portions. The inlet portion is usually integrated functionally with the right atrium ("atrialized portion"), while the other, including the trabecular and outlet portions, constitutes the functional right ventricle. The proximal atrialized right ventricle often has a wall thinner than the distal functional right ventricle, due to partial congenital absence of myocardium. An atrial septal defect is present in more than one-third of hearts, and the majority of the remainder has a patent foramen ovale resulting in a right-to-left shunt. The downward displacement of the septal tricuspid valve leaflet is associated with discontinuity of the central fibrous body and septal atrioventricular ring, thus creating a potential substrate for accessory atrioventricular connections and ventricular pre-excitation making the patient at risk of sudden death. Angiography has demonstrated that a significant number of patients with Ebstein's anomaly also have morphofunctional abnormalities of the left ventricle, which may be explained by increased fibrosis in the left ventricular wall and ventricular septum as demonstrated by histological studies. Regarding embryology, the leaflets and tensile apparatus of the tricuspid valve are believed to be formed mostly by a process of delamination of the inner layers of the inlet zone of the right ventricle. The downward displacement of the leaflets in Ebstein's anomaly suggests that delamination from the inlet portion failed to occur.

Adult↗
PubMed2000

Myocarditis mimicking acute myocardial infarction: role of endomyocardial biopsy in the differential diagnosis.

OBJECTIVE: To test the hypothesis, using endomyocardial biopsies, that unexplained cases of apparent acute myocardial infarction were caused by myocarditis. MATERIAL: Between 1992 and 1998, 12 patients were admitted to the coronary care unit with severe chest pain, ST segment elevation, increased serum creatine kinase and MB isoenzyme, and with wall motion abnormalities on echocardiogram highly suggestive of acute myocardial infarction. These patients were further investigated by endomyocardial biopsy, as their coronary angiograms were normal. A diagnosis of myocarditis was made according to the Dallas criteria. A panel of antibodies was used for immunohistochemical characterisation of inflammatory cell infiltrate. Polymerase chain reaction (PCR) was used to detect viral genomes in seven cases. RESULTS: Haematoxylin and eosin staining of the endomyocardial biopsy showed active myocarditis in six patients and borderline myocarditis in one. Immunohistochemistry was positive for inflammatory cell infiltrates in 11 patients, including all the seven who were positive on haematoxylin and eosin staining according to the Dallas criteria. Only one patient had no evidence of inflammation. PCR was positive in two patients, both for Epstein-Barr virus. Follow up showed complete resolution of echocardiographic abnormalities in all patients except one. CONCLUSIONS: Myocarditis can mimic acute myocardial infarction in patients with angiographically normal coronary arteries, leading to errors of treatment. In patients with apparent myocardial infarction and a normal coronary angiogram, endomyocardial biopsy may help in the diagnosis of myocarditis. The sensitivity of endomyocardial biopsy was enhanced by using immunohistochemical and molecular biological techniques.

Adult↗
PubMed2000

No detection of enteroviral genome in the myocardium of patients with arrhythmogenic right ventricular cardiomyopathy.

AIMS: Despite the evidence of familial occurrence, chromosomal gene mapping, and apoptosis as a mechanism of myocyte death, the aetiopathogenesis of arrhythmogenic right ventricular cardiomyopathy (ARVC) remains speculative. Because of the frequent histological finding of focal inflammatory infiltrates, the hypothesis of an infective myocarditis aetiology has been put forward. The aim of this investigation was to test this hypothesis. The presence of enteroviruses was investigated by a highly sensitive and specific molecular technique. METHODS: Endomyocardial tissue samples from 20 patients with ARVC (11 male, nine female; mean age, 40 years; SD, 16) and 20 control subjects with other cardiac diseases were analysed using reverse transcription and nested polymerase chain reaction (PCR). Myocardial samples obtained from four patients with enteroviral myocarditis and coxsackie B3 virus infected cells were used as positive controls. RESULTS: Endomyocardial biopsy was diagnostic for ARVC in all patients: myocardial atrophy was seen, with less than 45% residual myocytes. Foci of inflammatory infiltrates were seen in four biopsies, and the cells were identified by immunohistochemistry as mainly T cells. All samples, from both patients with ARVC and subjects with other cardiac diseases, were negative for enteroviral genome by means of nested PCR. CONCLUSION: These findings indicate that enteroviruses are not involved in the aetio-pathogenesis of ARVC. Future molecular studies should investigate the presence of other infective agents, as well as their possible role in triggering apoptosis.

Adult↗
PubMed1999

Histologic findings in the conduction system after cardiac transplantation and correlation with electrocardiographic findings.

The study of the sinus node and the specialized atrioventricular junction by serial sections in cardiac transplantation revealed that acute rejection involving the conduction system was equally severe as the working myocardium, with the exception of the His bundle. During acute rejection, the sudden appearance of a first-degree atrioventricular block may suggest severe involvement of the conduction system with impending cardiac arrest.

Adult↗
PubMed1999

Late potentials and ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy.

We studied 38 patients (mean age 32 +/- 14 years) with arrhythmogenic right ventricular cardiomyopathy (ARVC) to evaluate the clinical significance of histologic features on endomyocardial biopsy specimens as related to signal-averaged electrocardiography (SAECG), spontaneous ventricular arrhythmias, and hemodynamic features. Fifteen patients presented with ventricular tachycardia or fibrillation (sustained ventricular arrhythmias), 23 with other minor arrhythmias. SAECG variables and right ventricular ejection fraction (RVEF) were statistically correlated with the extent of myocardial fibrosis on biopsy in ARVC. An increased percentage of fibrous tissue (> or = 30%) was a significant univariate predictor of late potentials (p = 0.004) and reduced RVEF (p = 0.02). The 18 patients with late potentials had an increased percentage of fibrous tissue (p = 0.01), a reduced RVEF (p = 0.0004), and a higher risk for sustained ventricular arrhythmias (p = 0.05) than the 20 patients without late potentials. RVEF was the most powerful predictor of late potentials (p = 0.004) at multivariate analysis. Moreover, RVEF < or = 50% was associated with an increased risk for development of sustained ventricular arrhythmias (p = 0.02). A SAECG parameter, namely the root-mean-square voltage of the terminal 40 ms at 25 Hz, was an independent predictive factor for the occurrence of sustained ventricular arrhythmias (p = 0.02). Although fibrous tissue may contribute to delayed myocardial activation in ARVC, a reduced RVEF plays an essential role for spontaneous manifestation of sustained ventricular arrhythmias.

Adolescent↗
PubMed1999

Enteroviral genome in native hearts may influence outcome of patients who undergo cardiac transplantation.

The Enterovirus may be the most common agent responsible for viral myocarditis and cardiomyopathy. Very little of the literature is available concerning the follow-up of patients who underwent transplantation with enteroviral positivity in native hearts. In the present study, 45 explanted hearts from patients who underwent orthotopic heart transplant at University of Padova were studied by reverse transcriptase (RT)-polymerase chain reaction (PCR): 27 patients had dilated cardiomyopathy (DC), 12 had ischemic cardiopathy (IC), 2 had valvular disease (VD), 2 had arrhythmogenic right ventricular cardiomyopathy (ARVC), 1 had giant cell myocarditis (GCM), and 1 had lymphocytic myocarditis (LM). Two sets of PCR primers from the highly conserved region of Enterovirus and Rhinovirus were used. Samples of both ventricles and septum were analyzed in every patients. The RT-PCR and nucleotide sequencing of amplicons were also performed on all post-transplantation follow-up biopsies in patients with Enterovirus positivity in the native heart. The viral genome was detectable in only 1 of 27 patients with DC (3%) and in 1 patient with LM. Nucleotide sequence analysis of the amplified product showed differences in nucleotide sequence of PCR samples compared with the sequence of the coxsackievirus B3 used in the current study. The patient with Enterovirus-positive DC showed a higher index of severe rejection (>3A) in the first 6 months, compared with the other patients tested. The patient with Enterovirus-positive LM died of disease recurrence 2 months after transplantation. The present study reveals a scarce presence of Enterovirus in the myocardium of patients with chronic myocardial disease. Because Enterovirus infection was predictive of a poor prognosis in these two patients, molecular studies are useful in excluding viral involvement in native hearts of transplanted patients.

Adolescent↗
PubMed1999

Effective immunosuppressive therapy in a patient with primary pulmonary hypertension.

The case history is described of a young woman who presented with primary pulmonary hypertension and non-specific inflammatory signs. The patient received prolonged immunosuppressive treatment with low dose methotrexate and prednisone without any vasodilator agent. After one year the pulmonary artery pressure fell from a mean value of 47 mm Hg to 30 mm Hg and there was a corresponding clinical response. This case suggests that, in patients with pulmonary hypertension of unknown origin, immunopathogenetic factors should be sought in order to consider the utility of immunosuppressive therapy.

Adult↗
PubMed1999

Haemostatic abnormalities, cardiac involvement and serum tumor necrosis factor levels in X-linked dystrophic patients.

Left ventricular thrombosis and systemic emboli have been demonstrated to complicate cardiomyopathy in Duchenne and Becker muscular dystrophy (DMD, BMD). We investigated plasma levels of prothrombin fragment 1+2 (F1+2). thrombin-antithrombin III complex (TAT) and circulating levels of tumor necrosis factor-alpha (TNF-alpha), a procoagulant cytokine that has been shown to be elevated in patients with depressed cardiac function, in 20 patients with DMD and 12 patients with BMD as compared with 30 age-matched control subjects. Significantly elevated levels of F1+2 (DMD: 1.4+/-0.8 nmol/l; BMD: 1.8+/-0.8 nmol/l vs. controls: 0.7+/-0.2 nmol/l, p <0.01 and p <0.001, respectively), TAT complexes (DMD: 4.7+/-2.7 microg/l, BMD: 5+/-2.3 microg/l vs. controls: 1.6+/-0.5 microg/l, p <0.001) and TNF-alpha (54+/-9 vs. 25+/-7 pg/ml, p <0.001) were observed in patients with the dystrophic disease compared to control subjects. A significantly negative correlation was also found between F1+2 and TAT complexes and left ventricular ejection fraction (r = -0.65, p <0.0001; r = -0.80, p < 0.0001, respectively) and a positive correlation between F1+2 and TAT complexes and serum TNF-alpha levels (r = 0.67, p <0.0001; r = 0.70, p <0.0001, respectively). Our results indicate a hypercoagulable state in X-linked dystrophic patients. A possible relationship between haemostatic activation, left ventricular dysfunction and TNF-alpha system upregulation may be suggested.

Adolescent↗
PubMed1998

Cavopulmonary anastomosis in staging toward Fontan operation: pathologic substrates.

BACKGROUND: A review of the history and practice of cavopulmonary connections in staging toward Fontan operation and the pathologic experience at Padua University is presented. METHODS: Gross and histologic assessment of the heart-lung blocks removed at autopsy in the cases in which the cause of death could be related to a dysfunction of the cavopulmonary anastomosis were performed. RESULTS: The main complications were distortion of the intraatrial tunnel and thrombosis of the pulmonary branches of the cavopulmonary anastomosis. CONCLUSIONS: The cavopulmonary anastomosis remains a widespread procedure, both as a preliminary step to a Fontan operation and as an integral part of a Fontan or modified Fontan procedure in all those cardiac malformations characterized by a hypoplastic right or left ventricle in which these ventricles are too small to support the whole circulation.

Adolescent↗
PubMed1998

Transforming growth factor beta1 induces IL-1 receptor antagonist production and gene expression in rat vascular smooth muscle cells.

Atherosclerosis is an inflammatory-fibroproliferative process that may represent a possible milieu in which transforming growth factor-beta (TGF-beta) can be involved. Vascular smooth muscle cells (VSMC) may represent a source or a target of a large number of growth factors and proinflammatory cytokines, including interleukin-1 and its receptor antagonist (IL-1Ra). We tested the effect of TGF-beta1, on IL-1Ra production and gene expression in rat VSMC cultures. We found a significant dose (3-30 ng/ml) and time-dependent (0-48 h) increase in IL-1Ra immunoactivity in the supernatant of conditioned medium and cell lysates. The maximal effect was observed with TGF-beta at 30 ng/ml and after 24 h incubation time, respect to untreated cells (320 +/- 26 vs. 211 +/- 20 pg/ml; P < 0.01). Furthermore, TGF-beta1 induced an increased mRNA expression which began at 2 h and peaked at 18 h incubation time (about a 6-fold increase with respect to unstimulated cells). The effect of TGF-beta1 on IL-1Ra production was completely inhibited by an anti-IL-1beta antibody (10 microg/ml) (from 320 +/- 81 to 181 +/- 46 pg/ml). These experiments suggest that TGF-beta1, potentially produced in the vascular wall during atherogenesis, may play a pathophysiological role in the autocrine control of IL-1 actions, via VSMC IL-1Ra production.

Animals↗