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Biomedical subjects

A Gavazzi

Publications and source records attributed to A Gavazzi.

At least 19 recordsLinked to original sources
PubMed1992

Ventricular arrhythmias in dilated cardiomyopathy as an independent prognostic hallmark. Italian Multicenter Cardiomyopathy Study (SPIC) Group.

Prevalence and characteristics of ventricular arrhythmias (VA) on Holter monitoring were evaluated in 218 patients with invasively documented idiopathic dilated cardiomyopathy to clarify their relation to pump dysfunction, and their prognostic role. VA were observed in 205 patients (94%) and were high grade (ventricular pairs or tachycardia) in 130 (60%). No simple or multiform ventricular premature complexes were present in 88 patients (group 1; 41%), ventricular pairs in 63 (group 2; 32%), and ventricular tachycardia in 67 (group 3; 27%). Only echocardiographic right ventricular dimensions (p less than 0.05) and prevalence of VA during effort (8% in group 1, 15% in group 2, and 14% in group 3; p = 0.0005) differed significantly between groups. VA severity, and number of ventricular premature beats and tachycardia episodes were not correlated to right/left ventricular dimensions and pump function indexes. During a mean follow-up of 29 +/- 16 months, 27 patients died from cardiac events, and 16 received transplants. Three-year survival probability was lower in groups 2 (0.82) and 3 (0.81) than in group 1 (0.94). By Cox multivariate analysis, VA severity (p less than 0.01) was a major independent predictor of prognosis after markers of ventricular dysfunction such as left ventricular ejection fraction (p less than 0.001) and stroke work index (p less than 0.001).

Adolescent↗
PubMed1992

Search for Coxsackievirus B3 RNA in idiopathic dilated cardiomyopathy using gene amplification by polymerase chain reaction.

A polymerase chain reaction (PCR) amplification assay was developed to detect Coxsackievirus B3 ribonucleic acid (RNA) in blood and myocardial tissue of explanted hearts from 40 patients who underwent cardiac transplantation and in 1 normal heart. Twenty-one patients were affected by idiopathic dilated cardiomyopathy of different duration and 19 by coronary artery disease. Coxsackievirus B3 in vitro infected Vero cells and cells infected by related human enteroviruses (Coxsackievirus B2, B4, and poliovirus 1) were used as reaction controls. PCR was performed using 4 pairs of primers homologous to Coxsackie-virus B3 sequences. Three sets were located in regions of the genome conserved at nucleotide level between several enterovirus species (replicase gene, 5' noncoding region), while one was located in a Coxsackievirus B3-specific region (VP1 gene). Total RNA was prepared by acid guanidinium isothiocyanate extraction from tissue stored frozen at -80 degrees C. One microgram of total RNA was retrotranscribed with either antisense primer or with random hexanucleotide primers and then subjected to 40 cycles of amplification. PCR products were separated by electrophoresis on a 10% polyacrylamide gel, electrotransferred to a nylon membrane and then hybridized to oligonucleotide probes specific for the coxsackievirus B3 genome radiolabeled with radioactive isotope of phosphorous. All pairs of primers yielded specific amplification products when tested on Coxsackievirus B3-infected Vero cells, with a sensitivity of 1 infected cell out of 10(5) to 10(6) cells starting from 1 microgram total RNA. Primer sets for regions of Coxsackievirus B3 genome highly conserved between related enteroviral species gave positive amplification also when challenged with RNA from cells infected by Coxsackievirus B2, B4 and poliovirus 1.

Adult↗
PubMed1992

HLA and immunoglobulin polymorphisms in idiopathic dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) is an idiopathic heart muscle disorder. The presence of circulating cardiac antibodies and the association with HLA-DR4 are consistent with autoimmune pathogenesis in a subset of patients. Sixty-eight DCM patients and 277 controls were typed for IgG heavy-chain constant region (Gm) and kappa light-chain (Km) allotypes. All patients and 210 of the 277 controls were HLA-DR typed. The Gm (1, 3, 17; 23; 5*, 21, 28) phenotype was overrepresented in DCM compared with controls (25% vs 13%, p = 0.0139, pc = NS, RR = 2.23). The frequency of this phenotype was higher in patients with younger age at onset, shorter symptom duration, and among those who were positive for cardiac as well as for non-organ-specific autoantibodies than in controls. A higher frequency of the Gm (1, +/- 2, 3, 17; +/- 23; 5*, 21, 28) heterozygous phenotypes was also found in DCM compared to controls (40.91% vs 26.89%; p = 0.02, pc = 0.04, RR = 1.88). The finding of Gm heterozygosity in DCM was associated with serum positivity for cardiac antibodies. A higher proportion of DCM patients were positive for both the Gm (1, 3, 17; 23; 5*, 21, 28) phenotype and HLA-DR4 compared to normals (3/68 vs 0/210; p = 0.04, RR = 22.50).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Idiopathic dilated cardiomyopathy: lack of association between circulating organ-specific cardiac antibodies and HLA-DR antigens.

Organ-specific cardiac antibodies are serological markers of autoimmunity in dilated cardiomyopathy (DCM). HLA-DR4 and possibly DR5 are immunogenetic markers of susceptibility in DCM, but it is not known whether they are associated with autoantibody production. We studied the frequency of HLA-DR antigens and the presence of organ-specific cardiac antibodies in 80 DCM Caucasian patients from Northern Italy. HLA-DR typing was performed by serology; 289 healthy blood donors from the same region were tested as controls. HLA-DR frequencies in DCM were also compared with VIII International Workshop control data for Italy. Cardiac antibodies were detected by indirect immunofluorescence on human heart. Skeletal muscle was used to identify cross-reacting antibodies. The prevalence of cardiac antibodies in DCM was: organ-specific 34% and skeletal muscle cross-reactive 30%. The previously reported positive association between DCM and HLA-DR4 was confirmed using either the controls from the same region (21.25% vs 10.73% p = 0.02, relative risk = 2.30) or from all of Italy (21.25% vs 12.3%, p = 0.03). HLA-DR5 frequency was slightly but not significantly higher in DCM than in controls from the same region (46.25% vs 31.49% p = 0.02, relative risk of 1.87, p corrected = NS) or from all of Italy (46.25% vs 35.8% p = NS). HLA-DR3 frequency was lower in DCM than in controls from the same region (12.50% vs 29.41% p = 0.003, relative risk of 0.36, p corrected = 0.03). This negative association was not confirmed using the control data from the whole of Italy (12.50% vs 16.5% p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Histopathologic and molecular profile of human cytomegalovirus infections in patients with heart transplants.

From November 1985 to December 1990, 2,552 endomyocardial biopsy specimens from 209 heart transplant patients were studied. Forty-four (21%) patients developed 45 episodes of major human cytomegalovirus infection (HCMV). Human cytomegalovirus infection was primary in 13 of 44 patients. Thirty-one patients developed episodes of recurrent major infection. One patient had both primary and recurrent infections. Conventional histopathologic and immunohistochemical study, in situ hybridization, and polymerase chain reaction were used to diagnose HCMV myocardial involvement on corresponding endomyocardial biopsy specimens performed during infection. Conventional morphologic study showed typical viral inclusion bodies in four biopsy specimens. Two cases had myocyte HCMV localization with necrotizing myocarditis, whereas two had endothelial cell involvement without any inflammatory reaction. In these four biopsy specimens, immunohistochemistry showed a higher number of infected cells than that recognized by conventional histopathologic study. In situ hybridization detected infected cells with no evidence of cytopathic effect. Polymerase chain reaction gave HCMV amplification products in two additional biopsy specimens otherwise interpreted as moderate and mild rejection, respectively. Therefore, 6 biopsies showed HCMV myocardial involvement (6 of 45; 13.3%): all were from patients with primary HCMV infection (6 of 13; 46%). None of 32 major recurrent infections showed any myocardial involvement. In conclusion, our study is the first to demonstrate that myocardial HCMV involvement preferentially occurs in primary infection and HCMV endothelial localization can be free from inflammatory reaction, whereas HCMV myocyte localization leads to necrotizing myocarditis. Polymerase chain reaction has a higher diagnostic sensitivity than in situ hybridization. However, polymerase chain reaction findings of HCMV DNA on otherwise negative endomyocardial biopsy specimens remains of questionable significance because polymerase chain reaction-positive biopsy samples do not necessarily indicate tissue infection. It is impossible to determine whether amplified sequences derive from circulating leukocytes or from tissue cells.

Antigens, Viral↗
PubMed1992

[HLA polymorphism in the susceptibility or resistance to dilated cardiomyopathy].

Much of the surrounding studies on the association between HLA and diseases reflects a new insight into the key role of HLA molecules in the generation and regulation of the immune response. HLA molecules, on the surface of antigen presenting cells, bind foreign peptides. This HLA-antigen complex is then recognized by T lymphocytes and triggers the alloresponse against the peptide. Since many diseases associated with peculiar HLA antigens are thought to be autoimmune, the idea that certain Major Histocompatibility Complex (MHC) molecules could form complexes with self-peptides in anomalous ways, leading to an autoimmune reaction, is particularly attractive. Recent advances in molecular technology, x-ray crystallography and DNA studies have allowed the determination of the three-dimensional structure of some HLA class I and II molecules and also the amino acid sequences involved in binding of antigen fragments. This new information has prompted a search for differences, at the amino acid level, between HLA alleles previously shown to be positively or negatively associated with a pathology. Our own experience on the immunogenetic aspect of dilated cardiomyopathy (DCM) allowed us to assess some predisposing (HLA-DR4, DR5, C4A4) and protective (HLA-DR3) factors for DCM. Clinical heterogeneity also seems to imply a peculiar genetic background. The actual research is addressed to the study of the antigen binding site sequences and to the consideration of other new loci such as those entrapped within the HLA class III subregion (HSP70) and those lying within the class II region (PSF).

Cardiomyopathy, Dilated↗
PubMed1992

Endomyocardial biopsy of normal donor hearts before cardiac transplantation. A morphological and morphometrical study in 97 cases.

Endomyocardial biopsies from 97 normal donor hearts were examined. Morphometric analysis showed: mean myocyte diameter 22.21 +/- 6.93 mu, mean nuclear dimension 7.32 +/- 2.33 mu, mean nuclear/sarcoplasmic ratio 0.33 +/- 0.02. 31 biopsies showed enlarged myocytes (mean diameter 31.65 +/- 3.98 mu) with increased nuclear size (mean 10.45 +/- 1.39 mu), but preserved nuclear/sarcoplasmic ratio (mean 0.33 +/- 0.01). The mean age of these latter subjects was significantly higher. Endocardial thickness mean value was 17.73 +/- 4.58 mu, but in 28 cases the value exceeded the considered upper normal limit of 20 mu. Interstitial mononuclear cells were rare and randomly present. Interstitial fibrosis was observed in 15% and focal fibrosis in 27% of cases. Our results show that histology of biopsies from clinically normal hearts can widely vary, sometime overriding the pathologic boundaries. These apparently "benign" abnormalities should be kept in mind when specific pathologic substrates of cardiac diseases have to be defined.

Adolescent↗
PubMed1991

[Coronary disease of transplanted heart: prevalence, angiographic and etiopathogenetic aspects].

Progressive coronary artery disease is the most important factor influencing late mortality after heart transplantation. The aim of the study was to evaluate prevalence and clinical and angiographic findings of accelerated atherosclerosis in cardiac transplanted patients. During the first 5 years of the Heart Transplant Clinical Program at Policlinico S Matteo, Pavia, 81 patients underwent 156 coronary angiographies. The immunosuppressive therapy was based on cyclosporine, azathioprine and steroids; in some patients a reduced immunosuppressive schedule was started because of the presence of adverse effects. Coronary angiographies were performed in 68 patients after 1 year, in 40 patients after 2 years, in 19 patients after 3 years and in 18 patients after 4 years. The presence of coronary artery disease was defined by the angiographic occurrence of any decrease in the luminal diameter (including minor irregularities): according to these criteria coronary artery disease was found in 29 angiographies, performed in 13 patients, with a prevalence of 16% (13/81). An evaluation of the annual incidence showed respectively 14.7% at 1 year, 22.5% at 2 years, 31.5% at 3 years, 22.2% at 4 years. Coronary artery disease involvement was predominantly monovascular (56%) after 1 year and with a multivessel expression in the following years (2-vessel disease 33%, 3-vessel disease 50%). The major clinical problems in the transplanted patients with coronary artery disease were 3 deaths, related with heart failure in 2 cases and with sudden death in 1 case, and a new transplantation procedure in 2 patients. Prevalence and incidence of coronary artery disease observed after heart transplantation in this population were similar to those reported by other Authors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

[Endomyocardial biopsy in the heart transplant patient: the state of the art].

Data regarding 2176 endomyocardial biopsies (EMB) (Nov. '85-Dec. '89) performed in 164 transplanted hearts (4 etherotopic) from 158 patients (6 retransplants) are herein reported. This study was aimed to evaluate: 1) Incidence and characteristics of early ischemic myocardial damage. 2) The influence of different immunosurveillance protocols on incidence, degree and aggressiveness of acute rejection and the inflammatory infiltrate composition. 3) The immunophenotype of infiltrating cells in moderate acute rejection episodes. 4) HLA-DR antigen expression on myocyte sarcolemma. 5) Characterization of cells expressing immune response mediators. 6) Myocardial localization of opportunistic infections. 7) Useful information on chronic rejection. Our results demonstrate that: a) Mild rejection seldom progresses to moderate degree. b) Different immunosuppressive protocols can influence the incidence of acute rejection: in fact, in OKT3 protocol, the incidence of rejection episodes is higher than in other protocols as well as aggressiveness toward myocytes. c) Infiltrating cells maintain T lymphocyte prevalence with minor amounts of B lymphocytes and macrophages in the 3 different protocols. T cell subset characterization showed a slight prevalence of CD8 bearing cells over CD4 positive cells whereas CD57 cells were few and scattered. d) Class II Major Histocompatibility Complex (HLA-DR) expression never occurs on myocyte sarcolemma. e) TNF alpha is expressed in acute cardiac rejection by immunologically activated T lymphocytes and macrophages and the number of immunoreactive cells increases with progression of the rejection. f) Human cytomegalovirus infections can be primary or recurrent. Myocardial involvement has been observed in primary forms. Virus can affect endothelial cells (with no inflammatory reaction) or myocytes (myocarditis) and its diagnosis requires a combination of immunohistochemical and molecular biology techniques. Diagnosis of Toxoplasma gondii infection can be usually accomplished by routine histopathological study. g) Chronic rejection diagnosis is rarely based on biopsy derived information.

Biopsy↗
PubMed1991

Expression of tumor necrosis factor in human acute cardiac rejection. An immunohistochemical and immunoblotting study.

The authors performed an immunohistochemical study on expression of tumor necrosis factor alpha (TNF alpha) in endomyocardial biopsies from human cardiac allografts. TNF alpha immunoreactivity was found in 45% biopsies with mild acute rejection, in 83% biopsies with focal moderate rejection, in 80% biopsies with diffuse moderate rejection. Biopsies with absent rejection did not show immunoreactive cells. In mild rejection, positive cells were few and scanty monocytes and macrophages (MAC-387 and LN5 positive cells) and T lymphocytes (UCHL-1/CD45 RO positive cells) (up to 20% of all infiltrating cells). Expression of major histocompatibility complex (MHC) class II antigens on infiltrating and endothelial cells occurred earlier and independent of TNF alpha reactivity. Number of immunoreactive cells increased in moderate rejection (up to 50%). Immunoreactivity was also present in nonpigmented macrophages in part of the biopsies with resolving rejection (45%). The authors conclude that TNF alpha is expressed in acute cardiac rejection by immunologically activated inflammatory cells. Immunoreactive cells increase in number with increasing severity of the reaction.

Biopsy↗
PubMed1990

Expression of natriuretic peptide in ventricular myocardium of failing human hearts and its correlation with the severity of clinical and hemodynamic impairment.

Atrial natriuretic peptide (ANP) was immunohistochemically investigated in (1) right ventricular endomyocardial biopsy specimens from 87 apparently healthy donor hearts taken from victims of cerebral accidents; (2) 1 normal heart not suitable for transplantation (HBsAg carrier); (3) right ventricular endomyocardial biopsy specimens from 151 patients with dilated cardiomyopathy (DC); and (4) 57 explanted hearts, 26 with DC and 31 with ischemic heart disease. No ANP immunoreactivity was found in normal ventricles. Failing hearts showed ventricular positivity in 31% of the DC biopsy series, in 61% of the left ventricles, and in 30% of the right ventricles of the explanted heart series. An endoepicardial gradient was observed, because ANP positivity was greater and more extensive in the subendocardial layers. Ultrastructural studies were performed on biopsy specimens from 10 normal hearts and 132 DC biopsy samples. No ANP-storing granules were found in biopsy samples of normal ventricles, whereas ANP granules were seen in 15 of 132 (11.4%) DC cases. In parallel immunoblotting, investigation showed the same 13 kDa band protein in 1 normal atrium as well as in 8 failing atria and ventricles. ANP immunoreactivity was positively correlated with higher New York Heart Association functional classes as well as with higher left ventricular end-diastolic pressure (p less than 0.005), end-diastolic volume (p less than 0.005) and end-diastolic volume index (p less than 0.005). In conclusion, apparently healthy ventricles do not show ANP immunoreactivity, whereas failing ventricles do. ANP expression seems to be independent of the underlying disease, but positively related to the clinical status and the degree of left ventricular impairment and dilatation.

Adult↗
PubMed1990

[Evaluation of the effects of vasodilator therapy in primary pulmonary hypertension. Experience in 7 cases].

Primary pulmonary hypertension is an uncommon but serious disease that often results in debilitating symptoms and early death. One approach to treatment has been to attempt a reduction of pulmonary artery pressure and vascular resistance by using vasodilator drugs with conflicting results in several studies. The aim of this study is to review the ten-years (1978-1988) experience of vasodilator therapy for primary pulmonary hypertension at our institute. In this period 7 patients, 5 women and 2 men, mean age 38.4 years (range 15-66) met clinical and hemodynamic criteria for primary pulmonary hypertension. At diagnosis 3/7 patients were in NYHA class III and 2/7 in class II. Diagnosis was confirmed by open lung biopsy in one case. Mean pulmonary artery pressure was 66 +/- 17 mmHg, mean value of pulmonary vascular resistances was 22.5 +/- 11 U.W. and of cardiac index 1.8 +/- 0.58 l/min/m2. Twelve different vasodilator drugs were tested during right heart catheterization in a non randomized manner. Various vasodilators were usually tested in the same patient (2 or more drugs in 6 patients). Only one patient did not tolerate acute therapy because of development of a persistent systemic hypotension. Hemodynamic responses to nitrates showed a general reduction in pulmonary artery pressure and pulmonary vascular resistances with marginal changes in cardiac index. Calcium channel-blocking agents elicited different responses in similar patients with favorable, little, no or adverse effects in pulmonary hemodynamics and sometimes a significant decrease in systemic vascular resistances. Also hydralazine showed favorable hemodynamic results in few cases but exacerbated pulmonary hypertension in others.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

The morphologic spectrum of dilated cardiomyopathy and its relation to immune-response genes.

Endomyocardial biopsies from 174 patients with dilated cardiomyopathy (DC) were examined. Eight patients with histologically proven myocarditis were excluded from the study. A peculiar pattern of oversized and bizarre nuclei was observed in only some of the remaining patients. Two groups were identified: those with and without this feature (groups A and B, respectively). Myocyte width, nuclear diameter and nuclear/sarcoplasmic ratio were significantly higher in group A. The mean respective values were 36 +/- 5 mu, 14 +/- 3 mu and 0.41 +/- 0.08 for group A versus 20 +/- 8 mu, 7 +/- 2 mu and 0.37 +/- 0.08 for group B. Interstitial fibrosis was similarly present in groups A and B. Endocardial thickness was significantly increased in all patients, with group A showing the highest mean value. The morphologic features showed no correlation with the clinical condition of the patients at time of presentation. HLA typing was performed in 50 consecutive patients, 38 from group A and 12 from group B. DR4 and DR5 antigens were significantly more frequent in DC patients than in a normal population control (400 blood donors), while DR3 was less frequent. Group A was more strongly associated with the DR5 antigen than group B (55.3 vs 25.0%, respectively). It was less strongly associated with the DR4 antigen compared with group B (21.5 vs 41.7%, respectively). No difference was observed between the 2 groups concerning negative association with the DR3 antigen. Endomyocardial biopsies from DC patients reveal marked morphologic changes from patient to patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Myocardial iron grading by endomyocardial biopsy. A clinico-pathologic study on iron overloaded patients.

Endomyocardial biopsy was performed in 13 patients with primary or secondary iron overload. Prussian blue staining showed visible iron in the biopsy fragments of 8 out of 13 patients. Because of the inhomogeneity of iron deposition in the biopsy fragments, a semi-quantitative myocardial iron grading system was used in which the percentage of Perls' positive cells on 4 to 6 biopsy fragments was averaged from each case. The presence of stainable iron in the myofibrils was not predictable from serum iron, transferrin saturation, serum ferritin or liver iron grading, nor from evidence of endocrine dysfunction. In patients with Perls' positive material in the myocardium, there was a significant correlation between the endomyocardial iron grade and serum iron and transferrin saturation. These results suggest that other factors besides the body iron load determine cardiac iron deposition. The fact that myocardial siderosis was documented only in patients with hepatic cirrhosis, irrespective of the hepatic iron load, suggests that severe liver damage may be a prerequisite for the accumulation of iron in the heart.

Adult↗
PubMed1989

[Progressive changes in the lymphocyte subpopulations and the clinical picture in 2 brothers with familial dilated cardiomyopathy].

We report two brothers, aged 22 and 34, affected by dilated cardiomyopathy. At the first examination both patients were in NYHA functional class I. Their echocardiograms showed dilated and hypokinetic ventricles. Their clinical condition remained stable for three years, during which the peripheral immunophenotyping of T-lymphocyte subsets showed T-helper/T-suppressor ratio values lower than normal (normal value for our laboratory = 1.64 +/- 0.53) due both to low T-helper and to high T-suppressor subsets. Subsequently, the clinical condition of both patients deteriorated, exercise tolerance decreased and echocardiographic ventricular diameters increased. T-helper/T-suppressor ratio progressively increased from the initial values of 0.8 and 0.42 to 2.5 and 2.24, respectively. A few months later, both patients died, one because of refractory heart failure and the other one suddenly. Histologic examination of myocardial tissue in one patient showed a diffuse necrotizing disease involving myocytes with focal lymphocyte infiltrates, granulation tissue and endocardial thrombosis. The reported data underline the importance of genetic and familial factors in the pathogenesis and evolution of dilated cardiomyopathies. The increasing T-helper/T-suppressor ratio value which matched the deterioration of the clinical status, is proposed as a useful evolutive and prognostic marker.

Adult↗